Direct parasitological tests are the preferred laboratory tests. The qPCR is the one to be used, because the qualitative one can be positive in asymptomatic patients. The qPCR is more sensitive and turns positive earlier than the direct parasitological methods.⁴⁰¹ Nests of *T. cruzi* amastigotes should be searched in all biopsies. The RCD is diagnosed by the identification of parasites in the peripheral blood by use of direct methods or qPCR, as already described, or *T. cruzi* identification in biopsies. The RCD should be considered in patients with unexplained fever, dermopathy, myocarditis, or encephalitis.

All infected recipients should be investigated once a year for the cardiac and digestive forms of CD. All individuals with RCD should be treated for 60 days with benznidazole (5mg/kg/ day), nifurtimox (8mg/kg/day) being the second choice. During treatment, parasitological tests should be performed weekly until two negative tests are obtained.⁹³⁴

It is worth emphasizing that serological tests are not useful for the diagnosis of RCD and that negative seroconversion has been reported in patients with chronic CD after being transplanted because of immunosuppression.⁹³¹

It is still uncertain whether the use of specific protocols of chemotherapy drugs can influence the RCD. Thus, avoiding the use of antithymocyte globulin and minimizing the use of mycophenolate seem recommendable. Some studies have suggested that mechanistic target of rapamycin (mTOR) inhibitors could favor the control of *T. cruzi* replication,⁹⁴¹ thus being a more appropriate regimen for patients at risk for CD. However, an optimal regimen has not been established.⁶⁵⁵

### 13.8.3. Autoimmune Diseases

The experience with CD associated with autoimmune diseases is scarce and limited mainly to case reports, most of them related to systemic lupus erythematosus.⁹⁴² Thus, surveillance for RCD and proper treatment are recommended. In addition, there is no evidence favoring the prophylactic use of benznidazole prior to corticosteroid at immunosuppressive dose. Monitoring possible RCD is the best management.

### 13.9. Chagas Disease and Aging

The combination of successful public policies to control CD transmission, the increase in life expectancy of Brazilians, and the improvement in housing conditions in endemic regions has changed the patients' profile, propitiating an increase in the mean age of *T. cruzi* chronically infected individuals.⁹²⁶,⁹⁴³ However, *T. cruzi* infection remains an independent predictor of all-cause mortality and stroke in the elderly.⁷⁰,⁸⁴⁹ These are new challenges for the care of patients with CD, when the degenerative diseases of the elderly, SAH, diabetes mellitus, dyslipidemia, and coronary artery disease, compound the injury to the heart caused by CD, thus influencing the prognosis and quality of life of that population.

At the same time, information on how CD presents in the elderly is scarce, because most longitudinal studies have been performed a long time ago in predominantly young populations.⁴⁰⁴ Cross-sectional studies conducted in the states of Ceará,⁹⁴⁴ São Paulo (city of Campinas),⁵²³ and Rio de Janeiro⁹²⁶ in elderly individuals with CD on outpatient care have reported SAH as the most frequent comorbidity.

In addition to SAH, other comorbidities have been reported, such as dyslipidemia, osteoporosis, osteoarthritis, diabetes mellitus, HF, coronary artery disease, hypothyroidism, dyspepsia, depression, stroke, and renal failure. Thus, those patients require special attention. Moreover, chronic comorbidities can result in frequent visits to the medical office and risk for drug interactions, adverse effects, and the daily use of five or more medications difficult to be correctly managed by the elderly.⁹⁴⁵

In the cross-sectional studies mentioned, cardiomyopathy was the predominant clinical form of CD; however, information on the prognostic value of the changes in the elderly is still scarce.⁹⁴⁶,⁹⁴⁷ In a study conducted in Bambuí, a cohort of elderly with and without CD, electrocardiographic changes were clearly more frequent in patients with CD.³⁰³ The ECG abnormalities significantly associated with CD were sinus bradycardia, frequent ventricular or supraventricular extrasystoles, AF, RBBB, LAFB, 1st-degree AVB, and prolonged QT interval.

The RBBB, especially when associated with LAFB, was strongly associated with the presence of CD, being observed in 40% of the population with CD and in only 8% of the elderly without CD. The ECG variables independently associated with increased risk of death in patients with CD were frequent ventricular or supraventricular extrasystoles, AF, RBBB, inactive electrical zone, primary alterations of ventricular repolarization, and LV hypertrophy. Those with normal ECG findings or mild changes did not have increased risk of death as compared to the noninfected population.³⁰³

Many elderlies do not have either an initial clinical assessment to classify CD or appropriate follow-up care and treatment. This can be seen in the cross-sectional study conducted in the endemic area of São João do Piauí, in the Brazilian semiarid region. That study has evidenced high prevalence of CD in the elderly, which reached up to 34% in the age group of 61-75 years and 39% in the age group over 75 years. In that region, despite the disease transmission control, the diagnosis and treatment were suspended, and many elderlies never had an initial clinical assessment. That region, as well as others with socioenvironmental characteristics similar to those of the Brazilian semiarid region, continues to suffer with the scarcity of PHC groups trained to diagnose and treat the population.⁹⁴⁸

Classical studies in endemic areas have shown that the IFCD is the most prevalent form of CD and that 30% to 40% of the individuals can indefinitely persist in that clinical form.³⁰⁰ In contrast, a study has reported that only 13% of the elderlies have normal ECG findings, suggesting that the severity of CD in the elderly can be similar to that in young adults.³⁰³,⁹⁴⁷ This information requires further investigation for substantiation and confirmation.

## 14. Recommendations for Implantation of Structured Health Services for the Follow-Up of Individuals with Chronic Cardiomyopathy of Chagas Disease

Considering the impact of social, economic, and cultural factors on the genesis and evolution of CCCD, its clinical management in healthcare services requires the formation of a care network in a model that transcends biomedical
dimensions. Thus, it should ensure access to comprehensive, hierarchical, and decentralized care, encompassing the social determination process that permeates this neglected disease, cause and consequence of structural poverty.

As already described, individuals with CCCD have high morbidity and mortality as compared to those with other cardiomyopathies. Most of them belong to underprivileged social classes and are highly vulnerable, which hinder their access to diagnosis and treatment.⁹⁴⁹ Regarding healthcare provision, the conditions of individuals with CCCD are usually critical, which include long treatment with a low rate of success, and late diagnosis, usually in advanced stages of disease.

In addition, patients with CCCD face bias and stigma in different social contexts, which compounds even more their not only physical, but psychological and social suffering. Chagas disease is among the most neglected diseases worldwide, especially in Latin America, according to the WHO. It is a challenging chronic condition for any public health system because the affected individuals can demand health actions from low/medium technological complexity, in approximately 70% to 80% of the cases (mainly in PHC), up to access to tertiary and quaternary care, increasing public health-related costs. It is worth emphasizing the critical negative impact on the quality of life of affected individuals, their families, and communities.⁹⁵⁰-⁹⁵²

In Brazil, from 2000 to 2010, the CCCD burden corresponded to a total of 7 402 559 potential years of life impaired, 9% of which due to years of life lost and 91% due to years lived with disability.⁹⁵³

The SUS, in its hierarchical and decentralized conception, has been designed to reach comprehensiveness as a referential, particularly for PHC territories, with support from the matrix, such as referral services for more complex cases. However, it requires investments in addition to qualified and engaged public management that enables the formation of a care network grounded in lines of care strongly integrated with health surveillance actions.

There are some factors that can explain the persistence of the sanitary gap experienced by individuals with CD, even 113 years after CD discovery. As an example of the cycle of negligence, CD affects a silent and silenced population that faces persistent science, market, and public health challenges.

Basic questions remain unanswered in the endemic context: Who are these individuals? Where are they? How are they?⁹⁵¹,⁹⁵⁴

In more complex clinical management contexts, when recommending the formation of structured services for the follow-up of individuals with CCCD, some aspects require attention, such as an appropriate outpatient space affiliated to a tertiary or quaternary hospital with cardiological assistance that can provide additional intermediary to high complexity tests for proper cardiac staging.

In addition, regarding access to better structured services, it is worth noting the need for follow-up of individuals living in challenging areas, such as the Amazonian region, rural areas, and urban peripheries. In such cases, the use of differentiated technological media, such as teleconsultation and remote ECG and chest X-ray reporting, might be necessary.

Structured health services in CCCD might become a regional and state reference for cases requiring more complex clinical management, aimed at diagnosis clarification and staging of organ impairment. In addition, those services might support state and municipal permanent education programs for PHC professionals (considering the entire health team), which include communitarian health and endemic combat agents, for the clinical management of CD, which, although endemic, is still underdiagnosed.

For a structured health service to be fully functional, it requires an interdisciplinary multiprofessional team, known as the best way to provide longitudinal and comprehensive care to chronic diseases. In addition to timely diagnosis and treatment, those diseases require rehabilitation and quaternary prevention.

When creating a health service dedicated to the management of individuals with CCCD, it is important to contemplate their peculiarities, understand their biopsychosocial context, and practice patient-centered, instead of disease- or organ-centered, medicine.

In that work model, the team should recognize the common elements that demand strong interaction between the professionals, as well as the work process specificities delimited by their acting possibilities and responsibilities. In addition, the team should have knowledge of CCCD, as well as its management, so that all can communicate well. This is meant to avoid distorted or untrue information.⁹⁵¹,⁹⁵⁵,⁹⁵⁶

A structured service for management of CCCD cases should ideally count on the following professionals: physicians (cardiology, internal medicine, infectious disease, gastroenterology), nurses, psychologists, nutritionists, pharmacists, physical therapists, physical educators, and social workers. The team can be enlarged with the adoption of new people responsible for other interventions, and its dimension should be adjusted to the local reality, the possibilities of each health service, and, most of all, the demands from affected individuals.⁹⁵¹,⁹⁵⁵

### 14.1. Assignments of Structured Health Services for the Follow-up of Individuals with Chronic Cardiomyopathy of Chagas Disease

1. Receive all cases proceeding from PHC units, secondary health care units [specialized emergency care units (UPAE)], cardiological and non-cardiological emergencies, maternity hospitals, public or private blood centers, transplant services, as well as HIV/AIDS specialized services, for CD diagnosis and staging;

2. The CD diagnosis confirmation requires qualified anamnesis, directed at the clinical epidemiological context, with serological confirmation, preferably by the LACEN;

3. According to the Ministry of Health Ordinance nº 1.061, from May 18, 2020, diagnosed chronic cases of CD must be reported (compulsory notification) to improve the INSS network organization for the chronic CD prevalence in Brazil (Brazilian Ministry of Health);⁹⁵⁷

4. Stage cardiac impairment, by use of additional tests, maintaining communication with the Basic Healthcare Units (UBS) and UPAE, in a decentralized way, to accomplish referral and counter-referral flow. Individuals with the IFCD or
# Guidelines

nonsignificant cardiac impairment can be followed up in the UBS close to their dwellings, thus reducing the demand for treatment in other centers;

5. Individuals with CD and indication for etiological treatment should be managed according to the recommendations in this guideline's specific chapter and followed up in a UBS as long as the health team is trained in the clinical management of these cases;⁹⁵⁷

6. Women at reproductive age should be educated about the possibility of congenital transmission of CD and contraceptive methods. If they want to get or are already pregnant, they should be followed up by the PHC team in association with a referral obstetrics service and be treated according to the current guidelines;⁹⁵⁷

7. Patients with CD and HF, complex arrhythmias, need for PM or ICD implantation or CTX should be followed up at a higher complexity service. In some cases, the use of MCSD might be necessary as a bridge to CTX or an alternative to CTX if with good results;⁸

8. Identify associated digestive organic and functional impairment, and, when present, treat or refer the patient to a CD specialized service;⁹⁵⁷

9. Treat comorbidities or assess the need to refer patients for medical assessment at specialized services;⁹⁵¹

10. Cardiac rehabilitation should be integrated into structured health services of care to individuals with CCCD because of the proven clinical benefit of supervised physical exercise for their health and quality of life;⁹⁵⁸

11. Individuals with difficulty to understand the prescriptions of the health team should be helped by a pharmacist from the multiprofessional team to clarify dosage, interval between doses, adverse events, drug interactions, and strategies;⁵⁵²

12. Provide permanent education (presential or virtual) to affected individuals, their families, and caregivers on the disease and selfcare to the timely identification of cardiac decompensation signs and symptoms, making a communication channel (for example, *DISC Chagas*, *DISC IC*) and social media information available. With the dissemination of cell phones and the internet, remote care has proven to be greatly important in the management of more severe patients who cannot wait for a consultation or for small adjustments, which has been confirmed during the COVID-19 pandemic;

13. Educate on intracardiac devices, their functions, and need for PM or ICD implantation, as well as CTX, aiming to eliminate myths and beliefs that can negatively impact on the quality of life and adhesion to the treatments proposed, as well as on the possibility to donate blood, organs, and tissues;⁹⁵¹

14. Value the knowledge of affected individuals about their own disease, inviting them to participate in educational meetings, enabling the exchange of experiences, potentiating autonomy and empowerment, and encouraging changes from a passive to an active behavior regarding their therapeutic process and demands;⁹⁵⁸

15. Promote group meetings with specific themes, such as nutritional aspects, physical activity, depression, rights of individuals with chronic diseases, medico-legal aspects, transportation aid, social security, sexuality, pregnancy, breastfeeding, myths and truth related to CD;⁹⁵¹

16. Provide psychological support to reduce stigma, self-prejudice, taboos, and inappropriate beliefs regarding CD. Provide information on the prevention of aggravating factors, such as alcohol, smoking, illicit and licit drugs;⁹⁵¹,⁹⁵⁸

17. Develop continuing education programs for health professionals, with specific focus on the CCCD characteristics, stimulating multiprofessional learning and research;⁹⁵¹,⁹⁵⁸

18. Identify, through active search and doctor-patient relationship deepening, other family members in the same context of risk for *T. cruzi* exposure (including the possibility of congenital transmission) and incorporate the confirmed cases to the health service to determine the treatment to be adopted;⁹⁵¹

19. Encourage and support the creation of new associations of individuals with CD aimed at their better integration, establishing an active and purposeful communication channel with society, particularly the scientific, political, and health community, regarding their right to health claims. This would represent a strong channel in the search for active citizenship to transform their pain and suffering into a political act;

20. Always support the fight against prejudice, such as the necessary exclusion of the adjective 'Chagasic', which belittles the individuals affected by the disease. In clinical practice, it means to replace the term 'Chagasic' by 'individual affected with CD';⁹⁵¹,⁹⁵⁴,⁹⁵⁹

21. Publicize the existence of the FINDECHAGAS federation, created in 2010, as well as of the '14th of April' as the CD World Day, recognized by the WHO in 2019;⁹⁵⁴

22. Create telemedicine services for medical consultations and reporting of additional tests, such as ECG and chest X-ray. Based on this remote assessment, refer selected cases for management at structured health services.

## 14.2. Expected Benefits of Structured Health Services for the Follow-up of Individuals with Chronic Cardiomyopathy of Chagas Disease

Structured referral services for the follow-up of individuals with CCCD will be able to confirm what has been described for other chronic diseases.⁹⁵⁵ Once structured, the service is expected to be able to provide:

* Strengthening of the relationship between health professionals and individuals with CD;

* Development of active listening of individuals with CD and counseling about CD;

* Updated knowledge on the disease for healthcare professionals and affected individuals;

* Means to favor adhesion to pharmacological and nonpharmacological treatment;

* Means to lower morbidity and mortality, thus reducing emergency visits and rehospitalizations;

* Positive impact on quality of life; several recent studies have emphasized this relevant concept supported by coherent data;⁴³,⁵¹⁵,⁹⁶⁰

* Stigma and prejudice reduction;
* Empowerment, autonomy, and motivation of affected individuals to develop self-care and search their rights (health, education);

* Reduction in public health costs.

Although the implantation of a structured service requires financial as well as technical and operational investments, its structuration in a healthcare network is believed to favorably impact medium- and long-term cost and effectiveness.

Briefly, the major mission of structured services is to promote care that favors the clinical, psychological, and social stability of all individuals with CD.

# 15. Definition of Severe Cardiopathy and Medico-Legal Assessment

## 15.1. Introduction

Chronic cardiomyopathy of Chagas disease, still prevalent in Brazil, can progress to HF, ventricular arrhythmias, electrical conduction disorders, stroke, and other thromboembolic, pulmonary, and systemic complications, which represent severe situations,⁷ sometimes with social and work implications.

The term “severe cardiopathy”, created by a multidisciplinary team, appeared for the first time in the Brazilian legislation in 1952 in the statute of the union civil servants, as the law 1711 (item 11, article 178). Severe cardiopathy was defined as “a disease that leads to a temporary or permanent reduction in the heart’s functional capacity, which can be life-threatening or prevent servants from doing their work activities”.⁹⁶¹ According to that document, the medico-legal expert had to rely on subjective data to conclude their diagnostic investigation. However, with the advances of medico-legal medicine, based on better knowledge of the clinical course and prognosis of patients with CCCD, in addition to advances related to complementary methods to diagnose cardiovascular dysfunction, the characterization of cardiopathy as a morbid entity has evolved, requiring diagnosis supported by strict clinical assessment and laboratory confirmation, according to the SBC II Brazilian Guideline on Severe Cardiopathy, published in 2006.⁹⁶²

## 15.2. Concept and Scope

The term “severe cardiopathy” can be found in several legal processes, according to the Federal Law nº 7713/1988, article 6th, item XIV.⁹⁶¹ Severe cardiopathy comprises a large group of illnesses and clinical conditions of cardiac origin, characterized by a significant reduction in the survival perspective or significant limitation in physical capacity or both. The typification of severe cardiopathy is mainly aimed at complying with work issues (such as disability retirement, changes in responsibility, and workplace adaptation) or providing financial benefits (release of FGTS and PIS/PASEP) and tax benefits (exemption from income tax as described in the normative ordinance Nº 1174/MD of the Defense Ministry Manual, of September 6, 2006, chapter III), or income increasing (25% increase in the retirement value due to conditions requiring a caregiver).

In addition, it is important to clarify that the severe cardiopathy *status* is only defined after no satisfactory response to the appropriate clinical or surgical treatment, when recommended, or when there is no satisfactory therapy, or, even if there is, it is not sufficient to change the individual's clinical condition and prognosis.

Occasional changes in additional tests do not automatically imply diagnosis of severe cardiopathy. The verification of functional limitations and prognostic assessment result from a comprehensive investigation and contextualization of the clinical scenario of a patient with cardiopathy. Among the major inclusion criteria in the roll of severe cardiopathies, complete clinical assessment should be ensured, to provide information on the patient's physical capacity and, in parallel, information on the estimated survival rate for the condition in question should be obtained.

Complete clinical assessment is obtained through medical consultation with detailed anamnesis and physical examination, complemented with tests, such as ECG, chest X-ray, Doppler ECHO, 24-hour Holter, exercise testing, or cardiopulmonary exercise testing. In specific situations, more sophisticated or invasive tests might be necessary, such as myocardial scintigraphy, CMRI, coronary CT angiography, or coronary angiography.⁹⁶³ The information on survival derives from the level of evidence of the risk of death, which can be obtained, in the specific case of CCCD, by using scores validated and published in specialized journals.⁴⁰⁸,⁴⁷⁴,⁹⁶⁴

## 15.3. Score to Predict the Risk of Death in Patients with Chronic Cardiomyopathy of Chagas Disease

The CCCD course is variable and unpredictable, and one of its presentations is death, which can either be sudden, due to HF progression or result from thromboembolic phenomena. Therefore, estimating the risk of death of patients with CCCD is a clinical challenge and has been facilitated with the introduction of a score developed with that purpose.

That is the score created by Rassi Jr. et al., published in 2006, when following up a cohort of 424 patients with CCCD.⁴⁰⁸ During the study period, approximately 8 years, 130 patients died. Those authors identified six variables associated with death: NYHA functional class III or IV = 5 points; evidence of cardiomegaly on chest X-ray = 5 points; global or segmental LV dysfunction on ECHO = 3 points; NSVT on 24-hour Holter = 3 points; low-voltage QRS on ECG in all frontal leads = 2 points; and male sex = 2 points. Based on this score, those authors defined three risk categories: low risk (0-6 points); intermediate risk (7-11 points); and high risk (12-20 points). The 10-year mortality in the three groups was 10%, 44%, and 84%, respectively.⁴⁰⁸

By using the RASSI score, the work of the medical expert can be easily parameterized, translating into numbers the patient's clinical reality. Thus, a RASSI score ≥ 12 points certainly indicates severe cardiopathy. However, it is worth noting that the SBC II Brazilian Guideline on Severe Cardiopathy, published in 2006,⁹⁶² which currently supports the medico-legal expert diagnosis of severe cardiopathy, is based rather on the patient's physical capacity/quality of life after usual therapeutic resources have failed, than on the risk prediction science.
Despite the importance of the clinical findings and functional class, the search for new prognostic tools to refine clinical data is fundamental to subsidize better medico-legal investigations and their conclusions.

The need for urgent review of that guideline is noticeable so that the usefulness of those scientific advances on the release of medico-legal investigative reports about patients with CD can be fully debated.

## 15.4. Clinical Aspects

The most characteristic clinical aspects of CCCD are congestive HF, complex ventricular arrhythmias requiring ICD implantation, thromboembolic phenomena, and severe impairment of liver and kidney functions secondary to the underlying heart disease. It is worth noting that it is crucial to assess the physical functioning of those patients regarding their life expectancy reduction despite the optimized therapeutic arsenal to classify them as having severe cardiopathy caused by CD.

## 15.5. Medico-Legal Expert Assessment

The medico-legal expert is a professional trained to assess and provide (or not) the status of severe cardiopathy to individuals who seek the social security to receive benefits because of their typification. To become an efficient medico-legal expert, in addition to an academic education in the health area, the professional must take training and specialization courses. There are several manuals for that correct practice. In addition, it involves embracing the law. Severe cardiopathy caused by CD is usually within the severe cardiopathy spectrum and supported by three laws, which refer to the following legal regimens: unified legal regimen (law nº 8.112/90); social security regimen (law nº 8.213/91); and taxation regimen (law nº 11.052/04).

From the didactical viewpoint, severe cardiopathy can be classified as follows: 1) acute cardiopathies, of rapid progression, that can gradually turn into chronic cardiopathies, characterized by the loss of patient's physical ability and of heart functional capacity; 2) chronic cardiopathies, characterized by progressive limitation of the physical aptitude and heart functional capacity, exceeding the limits of efficiency of the cardiac compensation mechanisms, regardless of the appropriate clinical and/or surgical treatment adopted; 3) chronic or acute cardiopathies requiring permanent inotropic pharmacological (dopamine, dobutamine) or mechanical (intra-aortic balloon, biopump) support; and 4) terminal cardiopathy, when life expectancy is extremely reduced, nonresponsive to any type of therapy.

Differently from the medical board, the medico-legal expert acting results from the routine work of one single expert, designated to assess whether the severe cardiopathy status applies to a certain individual. This function requires emotional balance (not to be influenced by aspects other than the specific criteria) and discernment (to extract the elements to support typification of the clinical findings amidst a large number of documents). The expert, based on the medical report and additional tests, reassesses the individual to validate or not the severe cardiopathy condition litigated. A LVEF lower than 40% on optimized medication, is usually one of the major functional parameters adopted. Usually, a more detailed assessment is necessary to investigate all aspects of

the clinical findings and of the additional tests because borderline situations occur, with discordance between clinical findings and diagnostic methods, divergent test results, or need for additional equally relevant data for a proper decision.

In cases of discordance or divergence in the criteria selected for classification, and having the expert denied the presence of the disease, the judicial pathway is the natural choice in the presence of sufficient documentation.

In addition to a RASSI score ≥ 12 points, other important information to indicate the possible diagnosis of severe cardiopathy in patients with CCCD is as follows: isolated NYHA functional class III or IV; repeated episodes of syncope with no possibility of definitive control; presence of VT, mainly if symptomatic or requiring emergency care; marked cardiomegaly; and presence of cardiac thrombus or previous thromboembolic episodes.⁹⁶⁵

It is worth noting that the presence of symptomatic sinus node dysfunction or advanced AVB (Mobitz II, 3:1, 4:1, etc, and TAVB) not necessarily implies permanent functional limitation, because PM implantation might reverse the clinical findings and significantly improve the prognosis, particularly when those alterations occur in isolation. However, in CCCD, mainly in advanced stages, bradyarrhythmias and advanced blocks associated with myocardial dysfunction or complex ventricular arrhythmias are common, indicating more severe impairment. In such cases, a comprehensive cardiac assessment, as previously suggested, allows the medico-legal expert to identify the patient's actual situation in terms of definitive limitation, regarding both function and prognosis.

Similarly, the mere presence of positive serology for CD or its association with an electrocardiographic change, such as RBBB, is not sufficient to characterize severe cardiopathy. Although some of those individuals are known to progress to disabling forms, most can remain for decades in that stage, without symptoms, or even complete their life without clinical worsening.

For the medico-legal investigation to be fully evaluated, the assistant physician should issue detailed reports describing precisely and clearly the patient's clinical findings and add the tests that confirm the diagnosis.

## 15.6. Conclusion

The definition of severe cardiopathy is currently facilitated by advances of the knowledge on parameterized clinical evolution, clinical therapy, and additional tests, most of them with scientific support in terms of prognosis. This information, qualified and organized as scores developed in Brazilians, is highly valuable to support the medico-legal expert in their assessment. However, the physician's clinical rationale should be fully used to aggregate characteristic signs and symptoms, as well as data from the additional tests performed.

## Acknowledgements

We would like to express our gratitude to everyone involved in the management of the journals of the Brazilian Society of Cardiology, especially to Daniele Gullo for her excellent work at every stage of this project.
References

1. Andrade J P, Marin-Neto JA, Paola AA, Vilas-Boas F, Oliveira GM, Bacal F, et al. I Latin American Guidelines for the Diagnosis and Treatment of Chagas Cardiomyopathy. Arq Bras Cardiol. 2011;97(2 Suppl 3):1-48. doi: 10.1590/S0066-782X2011001600001.

2. Dias JC, Ramos AN Jr, Gontijo ED, Luquetti A, Shikanai-Yasuda MA, Coura JR, et al. Brazilian Consensus on Chagas Disease, 2015]. Epidemiol Serv Saude. 2016;25(spe):7-86. doi: 10.5123/S1679-49742016000500002.

3. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Consenso Brasileiro em Doença de Chagas. Rev Soc Bras Med Trop. 2005;38(Suppl III):1-29.

4. Gascón J, Albajar P, Cañas E, Flores M, Gómez i Prat J, Herrera RN, et al. Diagnosis, Management and Treatment of Chronic Chagas' Heart Disease in Areas Where Trypanosoma Cruzi Infection is Not Endemic. Rev Esp Cardiol. 2007;60(3):285-93.

5. Bern C, Montgomery SP, Herwaldt BL, Rassi A Jr, Marin-Neto JA, Dantas RO, et al. Evaluation and Treatment of Chagas Disease in the United States: A Systematic Review. JAMA. 2007;298(18):2171-81. doi: 10.1001/jama.298.18.2171.

6. Borracci RA, Cragno A, Roiter H, Galli A, Mollein D, Durante E, et al. Consenso de Enfermedad de Chagas-Mazza. Rev Argent Cardiol. 2011;79(6):544-64.

7. Nunes MCP, Beaton A, Acquatella H, Bern C, Bolger AF, Echeverría LE, et al. Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association. Circulation. 2018;138(12):e169-e209. doi: 10.1161/CIR.0000000000000599.

8. Brasil. Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Comissão Nacional de Incorporação de Tecnologias no SUS – CONITEC. Relatório 397 - Protocolo Clínico e Diretrizes Terapêuticas da doença de Chagas [Internet]. Brasília: Ministério da Sapude; 2018 [cited 2022 Out 7]. Available from: http://conitec.gov.br/images/Protocolos/Relatorio_PCDT_Doenca_de_Chagas.pdf.

9. Mitelman JE. Acuerdo Regional de los Expertos en Chagas de las Sociedades de Cardiologia Sudamericanas. Montevideo: Sociedad Sudamericana de Cardiologia; 2019.

10. Organización Panamericana de la Salud. Synthesis of Evidence: Guidance for the Diagnosis and Treatment of Chagas Disease. Rev Panam Salud Publica. 2020;44:e28. doi: 10.26633/RPSP.2020.28.

11. Benassi MD, Avayú DH, Tomasella MP, Valera ED, Pesce R, Lynch S, et al. Consenso Enfermedad de Chagas 2019. Rev Argent Cardiol. 2020;88(Suppl 8):1-74. doi: 10.7775/rac.es.v90.s1.

12. Mendoza I, Guiniger A, Kushni E, Sosa E, Velazzo V, Marques J, et al. Consensus of the Electrophysiology Committee of "USCAS" on the Treatment of Ventricular Arrhythmias in Chagas Disease. Arq Bras Cardiol. 1994;62(1):41-3.

13. Martinelli Filho M, Zimerman LI, Lorga AM, Vasconcelos JTM, Rassi A Jr. Diretrizes Brasileiras de Dispositivos. Cardíacos Eletrônicos Implantáveis (DCEI). Arq Bras Cardiol 2007;89(6):210-38.

14. Sociedad Argentina de Cardiologia. Consenso de Prevención Primaria y Secundaria de Muerte Súbita. Rev Argent Cardiol. 2012;80(2):165-8.

15. Fuganti CJ, Melo CS, Moraes AV Jr, Pachon-Mateos JC, Pereira WL, Galvão Filho SS, et al. Diretrizes Brasileiras de Dispositivos Cardíacos Eletrônicos Implantáveis. Relampa. 2015;28(2 Suppl):1-25.

16. Rohde LE, Montera MW, Bocchi EA, Clausell N, Albuquerque DC, Rassi S, et al. II Diretrizes da Sociedade Brasileira de Cardiologia para o Diagnóstico e Tratamento da Insuficiência Cardíaca. Arq Bras Cardiol. 1999;72(Suppl I):1-30.

17. Mesquita ET, Bocchi EA, Vilas-Boas F, Batlouni M. Revisão das II Diretrizes da Sociedade Brasileira de Cardiologia para o Diagnóstico e Tratamento da Insuficiência Cardíaca. Arq Bras Cardiol. 2002;79(Suppl 4):1-30.

18. Bocchi EA, Marcondes-Braga FG, Ayub-Ferreira SM, Rohde LE, Oliveira WA, Almeida DR, et al. Sociedade Brasileira de Cardiologia. III Diretriz Brasileira de Insuficiência Cardíaca Crônica. Arq Bras Cardiol. 2009;93(1 supl.1):1-71.

19. Bocchi EA, Marcondes-Braga FG, Bacal F, Ferraz AS, Albuquerque D, Rodrigues D, et al. Sociedade Brasileira de Cardiologia. Atualização da Diretriz Brasileira de Insuficiência Cardíaca Crônica - 2012. Arq Bras Cardiol. 2012;98(1 supl. 1):1-33.

20. Bacal F, Marcondes-Braga FG, Rohde LEP, Xavier JL Jr, Brito FS, Moura LZ, et al. 3º Diretriz Brasileira de Transplante Cardíaco. Arq Bras Cardiol. 2018; 111(2):230-89. doi: 10.5935/abc.20180153.

21. Rohde LEP, Montera MW, Bocchi EA, Clausell NO, Albuquerque DC, Rassi S et al. Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda. Arq Bras Cardiol. 2018;111(3):436-539. doi: 10.5935/abc.20180190.

22. Cursack G, Maidana G, Manfredi C, Huerta CM, Canella JPC, Blanchet MJ, et al. Consenso de Enfermedad de Chagas. Insuficiência Cardíaca em Miocardiopatia Chagásica Crónica. Insuf Card. 2019;14(1):12-33.

23. Rubin R. When Physicians Spread Unscientific Information About COVID-19. Jama. 2022;327(10):904-6. doi: 10.1001/jama.2022.1083.

24. Bazell R, Koh H, Bloom BR. The Tobacco Wars' Lessons for the Vaccination Wars. N Engl J Med. 2022;386(23):2159-61. doi: 10.1056/NEJMp2202618.

25. Marin-Neto JA. Doença de Chagas – Mais de 100 Anos Depois de sua Cientificamente Brilhante Descoberta, há Poucas Razões para se Comemorar? Revista USP. 2017;115:89-104. doi: 10.11606/issn.2316-9036.v0i115p89-104.

26. Hasslocher-Moreno AM. O ideal científica positivista no Brasil e a descoberta da doença de Chagas [undergraduate thesis]. Rio de Janeiro: Universidade Federal do Estado do Rio de Janeiro; 2021. doi: 10.13140/RG.2.2.32406.88645.

27. Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE Guidelines: A New Series of Articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64(4):380-2. doi: 10.1016/j.jclinepi.2010.09.011.

28. Packer M. Are Meta-Analyses a Form of Medical Fake News? Thoughts About How They Should Contribute to Medical Science and Practice. Circulation. 2017;136(22):2097-2099. doi: 10.1161/CIRCULATIONAHA.117.030209.

29. Institute of Medicine (US) Committee on Standards for Developing Trustworthy Clinical Practice Guidelines. Clinical Practice Guidelines We Can Trust. Graham R, Mancher M, Miller Wolman D, Greenfield S, Steinberg E, editors. Washington (DC): National Academies Press (US); 2011.

30. Rassi A Jr. Implantable Cardioverter-Defibrillators in Patients with Chagas Heart Disease: Misperceptions, Many Questions and the Urgent Need for a Randomized Clinical Trial. J Cardiovasc Electrophysiol. 2007;18(12):1241-3. doi: 10.1111/j.1540-8167.2007.01011.x.

31. Yeh RW, Valsdottir LR, Yeh MW, Shen C, Kramer DB, Strom JB, et al. Parachute Use to Prevent Death and Major Trauma When Jumping from Aircraft: Randomized Controlled Trial. BMJ. 2018;363:k5094. doi: 10.1136/bmj.k5094.

32. Bern C. Chagas' Disease. N Engl J Med. 2015;373(19):1882. doi: 10.1056/NEJMc1510996.

33. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância de Doenças e Agravos não Transmissíveis e Promoção da Saúde. Doenças Negligenciadas no Brasil: Vulnerabilidade e Desafios. In: Brasil. Ministério da Saúde. Saúde Brasil 2017: uma análise da situação de saúde e os desafios para o alcance dos objetivos de desenvolvimento sustentável Brasília (DF): Ministério da Saúde; 2018, p. 99-142.

34. Brasil. Ministério da Saúde. Doença de Chagas: 14 de abril – Dia Mundial. Bol Epidemiol. 2020;51:1-43.

35. Fonseca BP, Albuquerque PC, Zicker F. Neglected Tropical Diseases in Brazil: Lack of Correlation between Disease Burden, Research Funding and Output. Trop Med Int Health. 2020;25(11):1373-84. doi: 10.1111/tmi.13478.
# Guidelines

36. World Health Organization. Chagas Disease (American trypanosomiasis) [Internet]. Geneva: WHO; 2021 [cited 2022 Out 7]. Available from: https://www.who.int/en/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis).

37. Chagas C. Nova Tripanosomiase Humana. Estudos sobre a Morfologia e o Ciclo Evolutivo do Schizotrypanum cruzi n.g., n.sp., Agente Etiológico de Nova Entidade Mórbida do Homem. Mem Inst Oswaldo Cruz. 1909;1(2):159-218. doi: 10.1590/S0074-02761909000200008.

38. World Health Organization. Control of Chagas Disease: Second Report of the WHO Expert Committee. WHO Technical Report Series [Intenet]. Geneva: WHO; 2002 [cited 2022 Out 7]. Available from: https://apps.who.int/iris/bitstream/handle/10665/42443/WHO_TRS_905.pdf?sequence=1&isAllowed=y.

39. Organizacion Panamericana de la Salud. Estimación cuantitativa de la enfermedad de Chagas en las Americas. OP5/HDM/CD/425-0G 2006 [Internet]. Washington (DC): PAHO; 2006 [cited 2022 Out 7]. Available from: http://ops-uruguay.bvsalud.org/pdf/chagas19.pdf.

40. Gómez LJ, van Wijk R, van Selm L, Rivera A, Barbosa MC, Parisi S, et al. Stigma, Participation Restriction and Mental Distress in Patients Affected by Leprosy, Cutaneous Leishmaniasis and Chagas Disease: A Pilot Study in Two Co-Endemic Regions of Eastern Colombia. Trans R Soc Trop Med Hyg. 2020;114(7):476-82. doi: 10.1093/trstmh/trz132.

41. Echeverría LE, Marcus R, Novick G, Sosa-Estani S, Ralston K, Zaidel EJ, et al. WHF IASC Roadmap on Chagas Disease. Glob Heart. 2020;15(1):26. doi: 10.5334/gh.484.

42. Guhl F, Ramírez JD. Poverty, Migration, and Chagas Disease. Curr Trop Med Rep. 2021;8:52-8. doi: 10.1007/s40475-020-00225-y.

43. Almeida ILGI, Oliveira LFL, Figueiredo PHS, Oliveira RDB, Damasceno TR, Silva WT, et al. The Health-Related Quality of Life in Patients with Chagas Disease: The State of the Art. Rev Soc Bras Med Trop. 2022;55:e0657. doi: 10.1590/0037-8682-0657-2021.

44. Pan American Health Organization. Chronic Care for Neglected Infectious Diseases: Leprosy/hansen's Disease, Lymphatic Filariasis, Trachoma, and Chagas Disease [Internet]. Washington (DC): PAHO; 2020 [cited 2022 Out 7]. Available from: https://iris.paho.org/bitstream/handle/10665.2/53312/9789275122518_eng.pdf?sequence=1&isAllowed=y.

45. Heukelbach J, Sousa AS, Ramos AN Jr. New Contributions to the Elimination of Chagas Disease as a Public Health Problem: Towards the Sustainable Development Goals by 2030. Trop Med Infect Dis. 2021;6(1):23. doi: 10.3390/tropicalmed6010023.

46. Rassi AJr, Rassi A, Marin-Neto JA. Chagas Disease. Lancet. 2010;375(9723):1388-402. doi: 10.1016/S0140-6736(10)60061-X.

47. Santos EF, Silva AAO, Leony LM, Freitas NEM, Daltro RT, Regis-Silva CG, et al. Acute Chagas Disease in Brazil from 2001 to 2018: A Nationwide Spatiotemporal Analysis. PLoS Negl Trop Dis. 2020;14(8):e0008445. doi: 10.1371/journal.pntd.0008445.

48. Bruneto EG, Fernandes-Silva MM, Toledo-Cornell C, Martins S, Ferreira JMB, Corrêa VR, et al. Case-Fatality from Orally-transmitted Acute Chagas Disease: A Systematic Review and Meta-analysis. Clin Infect Dis. 2021;72(6):1084-92. doi: 10.1093/cid/ciaa1148.

49. Ramos NA Jr, Sousa AS. The Continuous Challenge of Chagas Disease Treatment: Bridging Evidence-Based Guidelines, Access to Healthcare, and Human Rights. Rev Soc Bras Med Trop. 2017;50(6):745-7. doi: 10.1590/0037-8682-0495-2017.

50. Lee BY, Bacon KM, Bottazzi ME, Hotez PJ. Global Economic Burden of Chagas Disease: A Computational Simulation Model. Lancet Infect Dis. 2013;13(4):342-8. doi: 10.1016/S1473-3099(13)70002-1.

51. Olivera MJ, Buitrago G. Economic Costs of Chagas Disease in Colombia in 2017: A Social Perspective. Int J Infect Dis. 2020;91:196-201. doi: 10.1016/j.ijid.2019.11.022.

52. Assis TM, Rabello A, Cota G. Economic Evaluations Addressing Diagnosis and Treatment Strategies for Neglected Tropical Diseases: An Overview. Rev Inst Med Trop Sao Paulo. 2021;63:e41. doi: 10.1590/S1678-9946202163041.

53. Bartsch SM, Avelis CM, Asti L, Hertenstein DL, Ndeffo-Mbah M, Galvani A, et al. The Economic Value of Identifying and Treating Chagas Disease Patients Earlier and the Impact on Trypanosoma cruzi Transmission. PLoS Negl Trop Dis. 2018;12(11):e0006809. doi: 10.1371/journal.pntd.0006809.

54. Pinheiro E, Brum-Soares L, Reis R, Cubides JC. Chagas Disease: Review of Needs, Neglect, and Obstacles to Treatment Access in Latin America. Rev Soc Bras Med Trop. 2017;50(3):296-300. doi: 10.1590/0037-8682-0433-2016.

55. Organização das Nações Unidas. Objetivos de Desenvolvimento Sustentável no Brasil [Internet]. New York: UN; 2021 [cited 2022 Out 7]. Available from: https://brasil.un.org/pt-br/sdgs.

56. Chaves GC, Arrieche MAS, Rode J, Mechali D, Reis PO, Alves RV, et al. Estimación de la Demanda de Medicamentos Antichagásicos: Una Contribución para el Acceso en América Latina. Rev Panam Salud Publica. 2017;41:45. doi: 10.26633/RPSP.2017.45.

57. Luquetti AO, Tavares SB, Siriano LR, Oliveira RA, Campos DE, Morais CA, et al. Congenital Transmission of Trypanosoma cruzi in Central Brazil. A study of 1,211 Individuals Born to Infected Mothers. Mem Inst Oswaldo Cruz. 2015;110(3):369-76. doi: 10.1590/0074-02760140410.

58. Silva GMS, Mediano MFF, Hasslocher-Moreno AM, Holanda MT, Sousa AS, Sangenis LHC, et al. Benznidazole Treatment Safety: The Médecins Sans Frontières Experience in a Large Cohort of Bolivian Patients with Chagas' Disease. J Antimicrob Chemother. 2017;72(9):2596-2601. doi: 10.1093/jac/dkx180.

59. Pan American Health Organization. Framework for Elimination of Mother-to-child Transmission of HIV, Syphilis, Hepatitis B, and Chagas [Internet]. Washington (DC): PAHO; 2017 [cited 2022 Out 7]. Available from: https://iris.paho.org/bitstream/handle/10665.2/34306/PAHOCHA17009-eng.pdf?sequence=1&isAllowed=y.

60. Pan American Health Organization. Guidelines for the Diagnosis and Treatment of Chagas Disease [Internet]. Washington (DC): PAHO; 2019 [cited 2022 Out 7]. Available from: https://iris.paho.org/bitstream/handle/10665.2/49653/9789275120439_eng.pdf?sequence=6&isAllowed=y.

61. Cajaiba-Soares AMS, Martinez-Silveira MS, Miranda DLP, Fernandes RCP, Reis MG. Healthcare Workers' Knowledge about Chagas Disease: A Systematic Review. Am J Trop Med Hyg. 2021;104(5):1631-38. doi: 10.4269/ajtmh.20-1199.

62. World Health Organization. Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021-2030 [Internet]. Geneva: WHO; 2020 [cited 2022 Out 7]. Available from: https://apps.who.int/iris/rest/bitstreams/1326801/retrieve.

63. World Health Organization. Chagas Disease in Latin America: An Epidemiological Update Based on 2010 Estimates. Wkly Epidemiol Rec. 2015;90(6):33-43.

64. Martins-Melo FR, Ramos AN Jr, Alencar CH, Heukelbach J. Prevalence of Chagas disease in Brazil: A Systematic Review and Meta-Analysis. Acta Trop. 2014;130:167-74. doi: 10.1016/j.actatropica.2013.10.002.

65. Capuani L, Bierrenbach AL, Alencar AP, Mendrone A Jr, Ferreira JE, Custer B, et al. Mortality Among Blood Donors Seropositive and Seronegative for Chagas Disease (1996-2000) in São Paulo, Brazil: A Death Certificate Linkage Study. PLoS Negl Trop Dis. 2017;11(5):e0005542. doi: 10.1371/journal.pntd.0005542.

66. Moncayo A, Silveira AC. Current Epidemiological Trends for Chagas Disease in Latin America and Future Challenges in Epidemiology, Surveillance and Health Policy. Mem Inst Oswaldo Cruz. 2009;104 Suppl 1:17-30. doi: 10.1590/S0074-02762009000900005.

67. Dias JCP. Human Chagas Disease and Migration in the Context of Globalization: Some Particular Aspects. J Trop Med. 2013;2013:789758. doi: 10.1155/2013/789758.

68. Dias JC, Silveira AC, Schofield CJ. The Impact of Chagas Disease Control in Latin America: A Review. Mem Inst Oswaldo Cruz. 2002;97(5):603-12. doi: 10.1590/S0074-02762002000500002.
69. Luquetti-Ostermayer A, Passos AD, Silveira AC, Ferreira AW, Macedo V, Prata AR. O Inquérito Nacional de Soroprevalência de Avaliação do Controle da Doença de Chagas no Brasil (2001-2008). Rev Soc Bras Med Trop. 2011;44(Suppl 2):108-21. doi: 10.1590/s0037-86822011000800015.

70. Lima-Costa MF, Peixoto SV, Ribeiro ALP. Chagas Disease and Mortality in Old Age as an Emerging Issue: 10 Year Follow-Up of the Bambuí Population-Based Cohort Study (Brazil). Int J Cardiol. 2010;145(2):362-3. doi: 10.1016/j.ijcard.2010.02.036.

71. Zaidel EJ, Forsyth CJ, Novick G, Marcus R, Ribeiro ALP, Pinazo MJ, et al. COVID-19: Implications for People with Chagas Disease. Glob Heart. 2020;15(1):69. doi: 10.5334/gh.891.

72. Hasslocher-Moreno AM, Saraiva RM, Brasil PEAAD, Sangenis LHC, Xavier SS, Sousa AS, et al. Temporal Changes in the Clinical-Epidemiological Profile of Patients with Chagas Disease at a Referral Center in Brazil. Rev Soc Bras Med Trop. 2021;54:e00402021. doi: 10.1590/0037-8682-0040-2021.

73. Martins-Melo FR, Carneiro M, Ramos AN Jr, Heukelbach J, Ribeiro ALP, Werneck GL. The burden of Neglected Tropical Diseases in Brazil, 1990-2016: A subnational Analysis from the Global Burden of Disease Study 2016. PLoS Negl Trop Dis. 2018;12(6):e0006559. doi: 10.1371/journal.pntd.0006559.

74. Martins-Melo FR, Ramos AN Jr, Alencar CH, Heukelbach J. Mortality from Neglected Tropical Diseases in Brazil, 2000-2011. Bull World Health Organ. 2016;94(2):103-10. doi: 10.2471/BLT.15.152363.

75. Simões TC, Borges LF, Assis ACP, Silva MV, Santos J, Meira KC. Chagas Disease Mortality in Brazil: A Bayesian Analysis of Age-Period-Cohort Effects and Forecasts for two Decades. PLoS Negl Trop Dis. 2018;12(9):e0006798. doi: 10.1371/journal.pntd.0006798.

76. Dias JC. Globalização, Iniquidade e Doença de Chagas. Cad Saude Publica. 2007;23(Suppl 1):13-22. doi: 10.1590/s0102-311x200700130003.

77. Schmunis GA, Yadon ZE. Chagas Disease: A Latin American Health Problem Becoming a World Health Problem. Acta Trop. 2010;115(1-2):14-21. doi: 10.1016/j.actatropica.2009.11.003.

78. Noller JMG, Froeschl G, Eisermann P, Jochum J, Theuring S, Reiter-Owona I, et al. Describing Nearly Two Decades of Chagas disease in Germany and the Lessons Learned: A Retrospective Study on Screening, Detection, Diagnosis, and Treatment of Trypanosoma cruzi Infection from 2000-2018. BMC Infect Dis. 2020;20(1):919. doi: 10.1186/s12879-020-05600-8.

79. Crowder LA, Wendel S, Bloch EM, O'Brien SF, Delage G, Sauleda S, et al. International Survey of Strategies to Mitigate Transfusion-Transmitted Trypanosoma cruzi in Non-Endemic Countries, 2016-2018. Vox Sang. 2022 Jan;117(1):58-63. doi: 10.1111/vox.13164.

80. Stokes AC, Lundberg DJ, Elo IT, Hempstead K, Bor J, Preston SH. COVID-19 and Excess Mortality in the United States: A County-Level Analysis. PLoS Med. 2021;18(5):e1003571. doi: 10.1371/journal.pmed.1003571.

81. Viljoen CA, Hoevelmann J, Muller E, Sliwa K. Neglected caRDIOVASCULAR diseases and their Significance in the Global North. Herz. 2021;46(2):129-37. English. doi: 10.1007/s00059-021-05020-7.

82. Navarro M, Reguero L, Subirà C, Blázquez-Pérez A, Requena-Méndez A. Estimating chagas disease Prevalence and Number of Underdiagnosed, and Undertreated Individuals in Spain. Travel Med Infect Dis. 2022;47:102284. doi: 10.1016/j.tmaid.2022.102284.

83. Almeida EA, Ramos NA Jr, Correia D, Shikanai-Yasuda MA. Co-infection Trypanosoma cruzi/HIV: systematic review (1980-2010). Rev Soc Bras Med Trop. 2011;44(6):762-70. doi: 10.1590/s0037-86822011000600021.

84. Shikanai-Yasuda MA, Mediano MFF, Novaes CTG, Sousa AS, Sartori AMC, Santana RC, et al. Clinical Profile and Mortality in Patients with T. cruzi/HIV Co-Infection from the Multicenter Data Base of the "Network for Healthcare and Study of Trypanosoma cruzi/HIV Co-Infection and Other Immunosuppression Conditions". PLoS Negl Trop Dis. 2021;15(9):e0009809. doi: 10.1371/journal.pntd.0009809.

85. Picado A, Cruz I, Redard-Jacot M, Schijman AG, Torrico F, Sosa-Estani S, et al. The Burden of Congenital Chagas Disease and Implementation of Molecular

Diagnostic Tools in Latin America. BMJ Glob Health. 2018;3(5):e001069. doi: 10.1136/bmjgh-2018-001069.

86. Carlier Y, Altcheh J, Angheben A, Freilij H, Luquetti AO, Schijman AG, et al. Congenital Chagas disease: Updated Recommendations for Prevention, Diagnosis, Treatment, and Follow-Up of Newborns and Siblings, Girls, Women of Childbearing Age, and Pregnant Women. PLoS Negl Trop Dis. 2019;13(10):e0007694. doi: 10.1371/journal.pntd.0007694.

87. Martins-Melo FR, Lima MS, Ramos AN Jr, Alencar CH, Heukelbach J. Prevalence of Chagas Disease in Pregnant Women and Congenital Transmission of Trypanosoma cruzi in Brazil: A Systematic Review and Meta-Analysis. Trop Med Int Health. 2014;19(8):943-57. doi: 10.1111/tmi.12328.

88. Howard EJ, Xiong X, Carlier Y, Sosa-Estani S, Buekens P. Frequency of the Congenital Transmission of Trypanosoma cruzi: A Systematic Review and Meta-Analysis. BJOG. 2014 Jan;121(1):22-33. doi: 10.1111/1471-0528.12396.

89. Fabbro DL, Danesi E, Olivera V, Codebó MO, Denner S, Heredia C, et al. Trypanocide Treatment of Women Infected with Trypanosoma cruzi and its Effect on Preventing Congenital Chagas. PLoS Negl Trop Dis. 2014;8(11):e3312. doi: 10.1371/journal.pntd.0003312.

90. Pan American Health Organization. Guia para Vigilância, Prevenção, Controle e Manejo Clínico da Doença de Chagas Aguda Transmitida por Alimentos [Internet]. Rio de Janeiro: PAHO; 2009 [cited 2022 Out 7]. Available from: https://bvsms.saude.gov.br/bvs/publicacoes/guia_vigilancia_prevencao_doenca_chagas.pdf.

91. Brasil. Ministério da Saúde. Territorialização e Vulnerabilidade para Doença de Chagas Crônica: 14 de abril – Dia Mundial de Combate à Doença de Chagas. Boletim Epidemiológico, 2022 [Internet]. Brasília: Ministério da Saúde; 2022 [cited 2022 Oct 01]. Available from: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/boletins-epidemiologicos/especiais/2022/boletim-especial-de-doenca-de-Chagas-numero-especial-abril-de-2022.

92. Barberia LG, Costa SF, Sabino EC. Brazil Needs a Coordinated and Cooperative Approach to Tackle COVID-19. Nat Med. 2021;27(7):1133-4. doi: 10.1038/s41591-021-01423-5.

93. Brasil. Ministério da Saúde. Guia de Vigilância em Saúde. 5th ed. [Internet]. Brasília: Ministério da Saúde; 2021 [cited 2022 Out 7]. Available from: https://bvsms.saude.gov.br/bvs/publicacoes/guia_vigilancia_saude_5ed.pdf.

94. Lima MM, Costa VMD, Palmeira SL, Castro APB. Estratificação de Territórios Prioritários para Vigilância da Doença de Chagas Crônica: Análise Multicritério para Tomada de Decisão em Saúde. Cad Saude Publica. 2021;37(6):e00175920. doi: 10.1590/0102-311X00175920.

95. Clark EH, Marquez C, Whitman JD, Bern C. Screening for Chagas Disease Should Be Included in Entry-to-Care Testing for At-Risk People with Human Immunodeficiency Virus (HIV) Living in the United States. Clin Infect Dis. 2022;75(5):901-6. doi: 10.1093/cid/ciac154.

96. Sliwa K, Singh K, Raspail L, Ojji D, Lam CSP, Thienemann F, et al. The World Heart Federation Global Study on COVID-19 and Cardiovascular Disease. Glob Heart. 2021;16(1):22. doi: 10.5334/gh.950.

97. Ehrenberg N, Ehrenberg JP, Fontes G, Gyapong M, Rocha EMM, Steinmann P, et al. Neglected Tropical Diseases as a Barometer for Progress in Health Systems in Times of COVID-19. BMJ Glob Health. 2021;6(4):e004709. doi: 10.1136/bmjgh-2020-004709.

98. Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, et al. Ethnic Differences in SARS-CoV-2 Infection and COVID-19-Related Hospitalisation, Intensive Care Unit Admission, and Death in 17 Million Adults in England: An Observational Cohort Study Using the OpenSAFELY Platform. Lancet. 2021;397(10286):1711-24. doi: 10.1016/S0140-6736(21)00634-6.

99. Castro MC, Kim S, Barberia L, Ribeiro AF, Gurzenda S, Ribeiro KB, et al. Spatiotemporal Pattern of COVID-19 Spread in Brazil. Science. 2021;372(6544):821-826. doi: 10.1126/science.abh1558.
# Guidelines

100. Mazzoli-Rocha F, Mendes FSNS, Silva PS, Silva GMSD, Mediano MFF, Sousa AS. Comprehensive Care for Patients with Chagas Cardiomyopathy During the Coronavirus Disease Pandemic. Rev Soc Bras Med Trop. 2020;53:e20200353. doi: 10.1590/0037-8682-0353-2020.

101. Alberca RW, Yendo TM, Ramos YÁL, Fernandes IG, Oliveira LM, Teixeira FME, et al. Case Report: COVID-19 and Chagas Disease in Two Coinfected Patients. Am J Trop Med Hyg. 2020 Dec;103(6):2353-6. doi: 10.4269/ajtmh.20-1185.

102. Hasslocher-Moreno AM, Saraiva RM, Silva GMSD, Xavier SS, Sousa AS, Costa ARD, et al. Chagas disease mortality during the coronavirus disease 2019 pandemic: A Brazilian referral center experience. Rev Soc Bras Med Trop. 2022;55:e0562. doi: 10.1590/0037-8682-0562-2021.

103. Diaz-Hernandez A, Gonzalez-Vazquez MC, Arce-Fonseca M, Rodriguez-Morales O, Cedillo-Ramirez ML, Caramarin-Lima A. Risk of COVID-19 in Chagas Disease Patients: What Happen with Cardiac Affectations? Biology. 2021;10(5):411. doi: 10.3390/biology10050411.

104. Molina I, Marcolino MS, Pires MC, Ramos LEF, Silva RT, Guimarães-Júnior MH, et al. Chagas Disease and SARS-CoV-2 Coinfection Does Not Lead to Worse In-Hospital Outcomes. Sci Rep. 2021;11(1):20289. doi: 10.1038/s41598-021-96825-3.

105. Mayoral LP, Hernández-Huerta MT, Papy-García D, Barritault D, Zenteno E, Navarro LMS, et al. Immunothrombotic Dysregulation in Chagas Disease and COVID-19: A Comparative Study of Anticoagulation. Mol Cell Biochem. 2021;476(10):3815-25. doi: 10.1007/s11010-021-04204-3.

106. Silva J, Ribeiro-Alves M. Social Inequalities and the Pandemic of COVID-19: The Case of Rio de Janeiro. J Epidemiol Community Health. 2021;75(10):975-9. doi: 10.1136/jech-2020-214724.

107. Fonseca EMD, Nattrass N, Lazaro LLB, Bastos FI. Political Discourse, denialism and Leadership Failure in Brazil's Response to COVID-19. Glob Public Health. 2021;16(8-9):1251-66. doi: 10.1080/17441692.2021.1945123.

108. Marinho MF, Torrens A, Teixeira R, Brant LCC, Malta DC, Nascimento BR, et al. Racial Disparity in Excess Mortality in Brazil During COVID-19 Times. Eur J Public Health. 2022;32(1):24-6. doi: 10.1093/eurpub/ckab097.

109. Brasil. Ministério da Saúde. Coordenação-Geral de Vigilância de Zoonoses e Doenças de Transmissão Vetorial. Nota informativa n. 9/2020-CGZV/DEIDT/ SVS/MS. Recomendações para Adequações das Ações de Vigilância e Cuidado ao Paciente com Doença de Chagas Frente à Situação Epidemiológica da COVID19 [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2022 Out 7]. Available from: https://antigo.saude.gov.br/images/pdf/2020/April/20/ SEI-25000.052809_2020_08-Nota-Informativa-Chagas-e-Covid-19.pdf.

110. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-Term Cardiovascular Outcomes of COVID-19. Nat Med. 2022;28(3):583-590. doi: 10.1038/s41591-022-01689-3.

111. Irish A, Whitman JD, Clark EH, Marcus R, Bern C. Updated Estimates and Mapping for Prevalence of Chagas Disease among Adults, United States. Emerg Infect Dis. 2022;28(7):1313-20. doi: 10.3201/eid2807.212221.

112. Abras A, Ballart C, Fernández-Arévalo A, Pinazo MJ, Gascón J, Muñoz C, et al. Worldwide Control and Management of Chagas Disease in a New Era of Globalization: A Close Look at Congenital Trypanosoma cruzi Infection. Clin Microbiol Rev. 2022;35(2):e0015221. doi: 10.1128/cmr.00152-21.

113. Ramos AN Jr, Souza EA, Guimarães MCS, Vermeij D, Cruz MM, Luquetti AO, et al. Response to Chagas disease in Brazil: Strategic Milestones for Achieving Comprehensive Health Care. Rev Soc Bras Med Trop. 2022;55:e01932022. doi: 10.1590/0037-8682-0193-2022.

114. Shikanai-Yasuda MA. Emerging and Reemerging Forms of Trypanosoma Cruzi Transmission. Mem Inst Oswaldo Cruz. 2022;117:e210033. doi: 10.1590/0074-02760210033.

115. Chevillard C, Nunes JPS, Frade AF, Almeida RR, Pandey RP, Nascimento MS, et al. Disease Tolerance and Pathogen Resistance Genes May Underlie Trypanosoma cruzi Persistence and Differential Progression to Chagas Disease Cardiomyopathy. Front Immunol. 2018;9:2791. doi: 10.3389/fimmu.2018.02791.

116. Junqueira C, Caetano B, Bartholomeu DC, Melo MB, Ropert C, Rodrigues MM, et al. The Endless Race between Trypanosoma Cruzi and Host Immunity: Lessons for and Beyond Chagas Disease. Expert Rev Mol Med. 2010;12:e29. doi: 10.1017/S1462399410001560.

117. Pereira IR, Vilar-Pereira G, Silva AA, Lannes-Vieira J. Severity of Chronic Experimental Chagas' Heart Disease Parallels Tumour Necrosis Factor and Nitric Oxide Levels in the Serum: Models of Mild and Severe Disease. Mem Inst Oswaldo Cruz. 2014;109(3):289-98. doi: 10.1590/0074-0276140033.

118. Daliry A, Pereira IR, Pereira PP Jr, Ramos IP, Vilar-Pereira G, Silvares RR, et al. Levels of Circulating Anti-Muscarinic and Anti-Adrenergic Antibodies and Their Effect on Cardiac Arrhythmias and Dysautonomia in Murine Models of Chagas Disease. Parasitology. 2014;141(13):1769-78. doi: 10.1017/S0031182014001097.

119. Ferreira RC, Ianni BM, Abel LC, Buck P, Mady C, Kalil J, et al. Increased Plasma Levels of Tumor Necrosis Factor-Alpha in Asymptomatic/"Indeterminate" and Chagas Disease Cardiomyopathy Patients. Mem Inst Oswaldo Cruz. 2003;98(3):407-11. doi: 10.1590/s0074-027620030000300021.

120. Pérez AR, Silva-Barbosa SD, Berbert LR, Revelli S, Belosar J, Savino W, et al. Immunoneuroendocrine Alterations in Patients with Progressive Forms of Chronic Chagas Disease. J Neuroimmunol. 2011;235(1-2):84-90. doi: 10.1016/j.jneuroim.2011.03.010.

121. Dutra WO, Menezes CA, Magalhães LM, Gollob KJ. Immunoregulatory Networks in Human Chagas Disease. Parasite Immunol. 2014;36(8):377-87. doi: 10.1111/pim.12107.

122. Cunha-Neto E, Chevillard C. Chagas Disease Cardiomyopathy: Immunopathology and Genetics. Mediators Inflamm. 2014;2014:683230. doi: 10.1155/2014/683230.

123. Abel LC, Rizzo LV, Ianni B, Albuquerque F, Bacal F, Carrara D, et al. Chronic Chagas' Disease Cardiomyopathy Patients Display an Increased IFN-Gamma Response to Trypanosoma Cruzi Infection. J Autoimmun. 2001;17(1):99-107. doi: 10.1006/jaut.2001.0523.

124. Gomes JA, Bahia-Oliveira LM, Rocha MO, Martins-Filho OA, Gazzinelli G, Correa-Oliveira R. Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease is Due to a Th1-Specific Immune Response. Infect Immun. 2003;71(3):1185-93. doi: 10.1128/IAI.71.3.1185-1193.2003.

125. Magalhães LM, Villani FN, Nunes MC, Gollob KJ, Rocha MO, Dutra WO. High Interleukin 17 Expression is Correlated with Better Cardiac Function in Human Chagas disease. J Infect Dis. 2013;207(4):661-5. doi: 10.1093/infdis/jis724.

126. Guedes PM, Gutierrez FR, Silva GK, Dellalibera-Joviliano R, Rodrigues GJ, Bendhack LM, et al. Deficient Regulatory T Cell Activity and Low Frequency of IL-17-Producing T Cells Correlate with the Extent of Cardiomyopathy in Human Chagas' Disease. PLoS Negl Trop Dis. 2012;6(4):e1630. doi: 10.1371/journal.pntd.0001630.

127. Souza PE, Rocha MO, Rocha-Vieira E, Menezes CA, Chaves AC, Gollob KJ, et al. Monocytes from Patients with Indeterminate and Cardiac forms of Chagas' Disease Display Distinct Phenotypic and Functional Characteristics Associated with Morbidity. Infect Immun. 2004;72(9):5283-91. doi: 10.1128/IAI.72.9.5283-5291.2004.

128. Machado FS, Koyama NS, Carregaro V, Ferreira BR, Milanezi CM, Teixeira MM, et al. CCR5 Plays a Critical Role in the Development of Myocarditis and Host Protection in Mice Infected with Trypanosoma Cruzi. J Infect Dis. 2005;191(4):627-36. doi: 10.1086/427515.

129. Silva GK, Costa RS, Silveira TN, Caetano BC, Horta CV, Gutierrez FR, et al. Apoptosis-Associated Speck-Like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1β Response and Host Resistance to Trypanosoma Cruzi Infection. J Immunol. 2013;191(6):3373-83. doi: 10.4049/jimmunol.1203293.

130. Stahl P, Ruppert V, Schwarz RT, Meyer T. Trypanosoma Cruzi Evades the Protective Role of Interferon-Gamma-Signaling in Parasite-Infected Cells. PLoS One. 2014;9(10):e110512. doi: 10.1371/journal.pone.0110512.
131. Sousa GR, Gomes JA, Damasio MP, Nunes MC, Costa HS, Medeiros NI, et al. The Role of Interleukin 17-Mediated Immune Response in Chagas Disease: High Level is Correlated with Better Left Ventricular Function. PLoS One. 2017;12(3):e0172833. doi: 10.1371/journal.pone.0172833.

132. Cai CW, Blase JR, Zhang X, Eickhoff CS, Hoft DF. Th17 Cells Are More Protective Than Th1 Cells Against the Intracellular Parasite Trypanosoma Cruzii. PLoS Pathog. 2016;12(10):e1005902. doi: 10.1371/journal.ppat.1005902.

133. Medina TS, Oliveira GG, Silva MC, David BA, Silva GK, Fonseca DM, et al. Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation. Front Immunol. 2017;8:1213. doi: 10.3389/fimmu.2017.01213.

134. Talvani A, Rocha MO, Barcelos LS, Gomes YM, Ribeiro ALP, Teixeira MM. Elevated Concentrations of CCL2 and Tumor Necrosis Factor-Alpha in Chagasic Cardiomyopathy. Clin Infect Dis. 2004;38(7):943-50. doi: 10.1086/381892.

135. Passos LS, Villani FN, Magalhães LM, Gollob KJ, Antonelli LR, Nunes MC, et al. Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8-T Cells and Modulates the Inflammatory Response in Patients with Chagas Heart Disease. J Infect Dis. 2016;214(6):935-44. doi: 10.1093/infdis/jiw266.

136. Costa RP, Gollob KJ, Fonseca LL, Rocha MO, Chaves AC, Medrano-Mercado N, et al. T-cell Repertoire Analysis in Acute and Chronic Human Chagas' Disease: Differential Frequencies of Vbeta5 Expressing T Cells. Scand J Immunol. 2000;51(5):511-9. doi: 10.1046/j.1365-3083.2000.00706.x.

137. Fernández-Mestre MT, Jaraquemada D, Bruno RE, Caro J, Layrisse Z. Analysis of the T-cell Receptor Beta-Chain Variable-Region (Vbeta) Repertoire in Chronic Human Chagas' Disease. Tissue Antigens. 2002;60(1):10-5. doi: 10.1034/j.1399-0039.2002.600102.x.

138. Menezes CA, Sullivan AK, Falta MT, Mack DG, Freed BM, Rocha MO, et al. Highly Conserved CDR3 Region in Circulating CD4(+)/Vβ5(+)/T Cells May be Associated with Cytotoxic Activity in Chagas Disease. Clin Exp Immunol. 2012;169(2):109-18. doi: 10.1111/j.1365-2249.2012.04608.x.

139. Gironès N, Cuervo H, Fresno M. Trypanosoma cruzi-induced Molecular Mimicry and Chagas' Disease. In: Oldstone MBA, editor. Molecular Mimicry: Infection-inducing Autoimmune Disease. Berlin: Springer-Verlag; 2005.

140. Passos LSA, Magalhães LMD, Soares RP, Marques AF, Alves MLR, Giunchetti RC, et al. Activation of Human CD11b⁺ B1 B-Cells by Trypanosoma cruzi-Derived Proteins Is Associated with Protective Immune Response in Human Chagas Disease. Front Immunol. 2019;9:3015. doi: 10.3389/fimmu.2018.03015.

141. Cordeiro FD, Martins-Filho OA, Rocha MOC, Adad SJ, Corrêa-Oliveira R, Romanha AJ. Anti-Trypanosoma cruzi Immunoglobulin G1 can be a Useful Tool for Diagnosis and Prognosis of Human Chagas' disease. Clin Diagn Lab Immunol. 2001;8(1):112-8. doi: 10.1128/CDLI.8.1.112-118.2001.

142. Pinto BF, Medeiros NI, Fontes-Cal TCM, Naziazeno IM, Correa-Oliveira R, Dutra WO, et al. The Role of Co-Stimulatory Molecules in Chagas Disease. Cells. 2018;7(11):200. doi: 10.3390/cells7110200.

143. Medeiros NI, Pinto BF, Elói-Santos SM, Teixeira-Carvalho A, Magalhães LMD, Dutra WO, et al. Evidence of Different IL-1β Activation Pathways in Innate Immune Cells from Indeterminate and Cardiac Patients with Chronic Chagas Disease. Front Immunol. 2019;10:800. doi: 10.3389/fimmu.2019.00800.

144. Menezes CA, Rocha MO, Souza PE, Chaves AC, Gollob KJ, Dutra WO. Phenotypic and Functional Characteristics of CD28+ and CD28- Cells from Chagasic Patients: Distinct Repertoire and Cytokine Expression. Clin Exp Immunol. 2004;137(1):129-38. doi: 10.1111/j.1365-2249.2004.02479.x.

145. Vitelli-Avelar DM, Sathler-Avelar R, Massara RL, Borges JD, Lage PS, Lana M, et al. Are increased Frequency of Macrophage-like and Natural Killer (NK) Cells, Together with High Levels of NKT and CD4+CD25high T Cells Balancing Activated CD8+ T Cells, the Key to Control Chagas' Disease Morbidity? Clin Exp Immunol. 2006;145(1):81-92. doi: 10.1111/j.1365-2249.2006.03123.x.

146. Fiuza JA, Fujiwara RT, Gomes JA, Rocha MO, Chaves AT, Araújo FF, et al. Profile of Central and Effector Memory T Cells in the Progression of

Chronic Human Chagas Disease. PLoS Negl Trop Dis. 2009;3(9):e512. doi: 10.1371/journal.pntd.0000512.

147. Cruz-Robles D, Vargas-Alarcón G, Ortíz-Muñiz R, Reyes PA, Monteon VM. Serum Cytokines and Activation ex vivo of CD4+ and CD8+ T Cells in Chagasic Chronic Mexican Patients. Ann Parasitol. 2017;63(4):299-308. doi: 10.17420/ap6304.116.

148. Villani FN, Rocha MO, Nunes MC, Antonelli LR, Magalhães LM, Santos JS, et al. Trypanosoma cruzi-Induced Activation of Functionally Distinct αβ and γδ CD4-CD8-T Cells in Individuals with Polar forms of Chagas' Disease. Infect Immun. 2010;78(10):4421-30. doi: 10.1128/IAI.00179-10.

149. Higuchi ML, Gutierrez PS, Aiello VD, Palomino S, Bocchi E, Kalil J, et al. Immunohistochemical Characterization of Infiltrating Cells in Human Chronic Chagasic Myocarditis: Comparison with Myocardial Rejection Process. Virchows Arch A Pathol Anat Histopathol. 1993;423(3):157-60. doi: 10.1007/BF01614765.

150. Reis MM, Higuchi ML, Benvenuti LA, Aiello VD, Gutierrez PS, Bellotti G, et al. An in Situ Quantitative Immunohistochemical Study of Cytokines and IL-2R+ in Chronic Human Chagasic Myocarditis: Correlation with the Presence of Myocardial Trypanosoma cruzi Antigens. Clin Immunol Immunopathol. 1997;83(2):165-72. doi: 10.1006/clin.1997.4335.

151. Cunha-Neto E, Dzau VJ, Allen PD, Stamatiou D, Benvenutti L, Higuchi ML, et al. Cardiac Gene Expression Profiling Provides Evidence for Cytokinopathy as a Molecular Mechanism in Chagas' Disease Cardiomyopathy. Am J Pathol. 2005;167(2):305-13. doi: 10.1016/S0002-9440(10)62976-8.

152. Fonseca SG, Reis MM, Coelho V, Nogueira LG, Monteiro SM, Mairena EC, et al. Locally Produced Survival Cytokines IL-15 and IL-7 may be Associated to the Predominance of CD8+ T Cells at Heart Lesions of Human Chronic Chagas Disease Cardiomyopathy. Scand J Immunol. 2007;66(2-3):362-71. doi: 10.1111/j.1365-3083.2007.01987.x.

153. Rodrigues DBR, Reis MA, Romano A, Pereira SA, Teixeira VP, Tostes S Jr, et al. In Situ Expression of Regulatory Cytokines by Heart Inflammatory Cells in Chagas' Disease Patients with Heart Failure. Clin Dev Immunol. 2012;2012:361730. doi: 10.1155/2012/361730.

154. Nogueira LG, Santos RH, Fiorelli AI, Mairena EC, Benvenuti LA, Bocchi EA, et al. Myocardial Gene Expression of T-bet, GATA-3, Ror-yt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-type Response. Mediators Inflamm. 2014;2014:914326. doi: 10.1155/2014/914326.

155. Gomes JA, Bahia-Oliveira LM, Rocha MO, Busek SC, Teixeira MM, Silva JS, et al. Type 1 Chemokine Receptor Expression in Chagas' Disease Correlates with Morbidity in Cardiac Patients. Infect Immun. 2005;73(12):7960-6. doi: 10.1128/IAI.73.12.7960-7966.2005.

156. Nogueira LG, Santos RH, Ianni BM, Fiorelli AI, Mairena EC, Benvenuti LA, et al. Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy are Controlled by Polymorphisms in CXCL9 and CXCL10. PLoS Negl Trop Dis. 2012;6(10):e1867. doi: 10.1371/journal.pntd.0001867.

157. Ferreira RR, Abreu RDS, Vilar-Pereira G, Degrave W, Meuser-Batista M, Ferreira NVC, et al. TGF-β Inhibitor Therapy Decreases Fibrosis and Stimulates Cardiac Improvement in a Pre-Clinical Study of Chronic Chagas' Heart Disease. PLoS Negl Trop Dis. 2019;13(7):e0007602. doi: 10.1371/journal.pntd.0007602.

158. Wan X, Wen JJ, Koo SJ, Liang LY, Garg NJ. SIRT1-PGC1α-NFκB Pathway of Oxidative and Inflammatory Stress During Trypanosoma cruzi Infection: Benefits of SIRT1-Targeted Therapy in Improving Heart Function in Chagas Disease. PLoS Pathog. 2016;12(10):e1005954. doi: 10.1371/journal.ppat.1005954.

159. Finsterer J, Kothari S. Cardiac Manifestations of Primary Mitochondrial Disorders. Int J Cardiol. 2014;177(3):754-63. doi: 10.1016/j.ijcard.2014.11.014.

160. Finsterer J, Frank M. Gastrointestinal Manifestations of Mitochondrial Disorders: A Systematic Review. Therap Adv Gastroenterol. 2017;10(1):142-54. doi: 10.1177/1756283X16666806.
161. Bocchi EA, Bestetti RB, Scanavacca MI, Cunha Neto E, Issa VS. Chronic Chagas Heart Disease Management: From Etiology to Cardiomyopathy Treatment. J Am Coll Cardiol. 2017;70(12):1510-24. doi: 10.1016/j.jacc.2017.08.004.

162. Wan X, Gupta S, Zago MP, Davidson MM, Dousset P, Amoroso A, et al. Defects of mtDNA Replication Impaired Mitochondrial Biogenesis During Trypanosoma cruzi Infection in Human Cardiomyocytes and Chagasic Patients: The Role of Nrf1/2 and Antioxidant Response. J Am Heart Assoc. 2012;1(6):e003855. doi: 10.1161/JAHA.112.003855.

163. Leme AM, Salemi VM, Parga JR, Ianni BM, Mady C, Weiss RG, et al. Evaluation of the Metabolism of High Energy Phosphates in Patients with Chagas' Disease. Arq Bras Cardiol. 2010;95(2):264-70. doi: 10.1590/s0066-782x2010005000099.

164. Teixeira PC, Santos RH, Fiorelli AI, Bilate AM, Benvenuti LA, Stolf NA, et al. Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy. PLoS Negl Trop Dis. 2011;5(6):e1205. doi: 10.1371/journal.pntd.0001205.

165. Ferreira LR, Frade AF, Baron MA, Navarro IC, Kalil J, Chevillard C, et al. Interferon-γ and Other Inflammatory Mediators in Cardiomyocyte Signaling During Chagas Disease Cardiomyopathy. World J Cardiol. 2014;6(8):782-90. doi: 10.4330/wjc.v6.i8.782.

166. Laugier L, Ferreira LRP, Ferreira FM, Cabantous S, Frade AF, Nunes JP, et al. miRNAs May Play a Major Role in the Control of Gene Expression in Key Pathobiological Processes in Chagas Disease Cardiomyopathy. PLoS Negl Trop Dis. 2020;14(12):e0008889. doi: 10.1371/journal.pntd.0008889.

167. Navarro IC, Ferreira FM, Nakaya HI, Baron MA, Vilar-Pereira G, Pereira IR, et al. MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes. PLoS Negl Trop Dis. 2015;9(6):e0003828. doi: 10.1371/journal.pntd.0003828.

168. Jha BK, Varikuti S, Seidler GR, Volpedo G, Satoskar AR, McGwire BS. MicroRNA-155 Deficiency Exacerbates Trypanosoma cruzi Infection. Infect Immun. 2020;88(7):e00948-19. doi: 10.1128/IAI.00948-19.

169. Zicker F, Smith PG, Netto JC, Oliveira RM, Zicker EM. Physical Activity, Opportunity for Reinfection, and Sibling History of Heart Disease as Risk Factors for Chagas' Cardiopathy. Am J Trop Med Hyg. 1990;43(5):498-505. doi: 10.4269/ajtmh.1990.43.498.

170. Deng X, Sabino EC, Cunha-Neto E, Ribeiro ALP, Ianni B, Mady C, et al. Genome Wide Association Study (GWAS) of Chagas Cardiomyopathy in Trypanosoma cruzi Seropositive Subjects. PLoS One. 2013;8(11):e79629. doi: 10.1371/journal.pone.0079629.

171. Casares-Marfil D, Strauss M, Bosch-Nicolau P, Lo Presti MS, Molina I, Chevillard C, et al. A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy. Clin Infect Dis. 2021;73(4):672-679. doi: 10.1093/cid/cia090.

172. Ouarhache M, Marquet S, Frade AF, Ferreira AM, Ianni B, Almeida RR, et al. Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease. J Clin Immunol. 2021;41(5):1048-63. doi: 10.1007/s10875-021-01000-y.

173. Marin-Neto JA, Simões MV, Rassi A Jr. Pathogenesis of Chronic Chagas Cardiomyopathy: The Role of Coronary Microvascular Derangements. Rev Soc Bras Med Trop. 2013;46(5):536-41. doi: 10.1590/0037-8682-0028-2013.

174. Rossi MA. Microvascular Changes as a Cause of Chronic Cardiomyopathy in Chagas' Disease. Am Heart J. 1990;120(1):233-6. doi: 10.1016/0002-8703(90)90191-y.

175. Rossi MA, Tanowitz HB, Malvestio LM, Celes MR, Campos EC, Blefari V, et al. Coronary Microvascular Disease in Chronic Chagas Cardiomyopathy Including an Overview on History, Pathology, and Other Proposed Pathogenic Mechanisms. PLoS Negl Trop Dis. 2010;4(8):e674. doi: 10.1371/journal.pntd.0000674.

176. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simões MV. Pathogenesis of Chronic Chagas Heart Disease. Circulation. 2007;115(9):1109-23. doi: 10.1161/CIRCULATIONAHA.106.624296.

177. Torres CM. Arteriosclerosis of the Fine Arterial Branches of the Myocardium (Chagas' coronaritis) & Focal Myocytolysis in Chronic Chagas' Heart Disease. Hospital. 1958;54(5):597-610.

178. Torres CM. Myocytolysis and Fibrosis of the Myocardium in Chagas' Disease. Mem Inst Oswaldo Cruz. 1960;58:161-82. doi: 10.1590/s0074-02761960000200004.

179. Higuchi ML, Fukasawa S, De Brito T, Parzianello LC, Bellotti G, Ramires JA. Different Microcirculatory and Interstitial Matrix Patterns in Idiopathic Dilated Cardiomyopathy and Chagas' Disease: A Three Dimensional Confocal Microscopy Study. Heart. 1999;82(3):279-85. doi: 10.1136/hrt.82.3.279.

180. Hagar JM, Rahimtoola SH. Chagas' Heart Disease in the United States. N Engl J Med. 1991;325(11):763-8. doi: 10.1056/NEJM199109123251103.

181. Hiss FC, Lascala TF, Maciel BC, Marin-Neto JA, Simões MV. Changes in Myocardial Perfusion Correlate with Deterioration of Left Ventricular Systolic Function in chronic Chagas' Cardiomyopathy. JACC Cardiovasc Imaging. 2009;2(2):164-72. doi: 10.1016/j.jcmg.2008.09.012.

182. Marin-Neto JA, Marzullo P, Marcassa C, Gallo L Jr, Maciel BC, Bellina CR, et al. Myocardial Perfusion Abnormalities in Chronic Chagas' Disease as Detected by Thallium-201 Scintigraphy. Am J Cardiol. 1992;69(8):780-4. doi: 10.1016/0002-9149(92)90505-s.

183. Simões MV, Pintya AO, Bromberg-Marin G, Sarabanda AV, Antloga CM, Pazin-Filho A, et al. Relation of Regional Sympathetic Denervation and Myocardial Perfusion Disturbance to Wall Motion Impairment in Chagas' Cardiomyopathy. Am J Cardiol. 2000;86(9):975-81. doi: 10.1016/s0002-9149(00)01133-4.

184. Rabelo DR, Rocha MO, Barros MV, Silva JL, Tan TC, Nunes MC. Impaired Coronary Flow Reserve in Patients with Indeterminate form of Chagas' Disease. Echocardiography. 2014;31(1):67-73. doi: 10.1111/echo.12364.

185. Oliveira LF, Romano MM, Carvalho EE, Cabeza JM, Salgado HC, Fazan R Jr, et al. Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy. J Am Heart Assoc. 2016;5(1):e002786. doi: 10.1161/JAHA.115.002786.

186. Oliveira LFL, Thackeray JT, Marin-Neto JA, Romano MMD, Carvalho EEV. Mejia J, et al. Regional Myocardial Perfusion Disturbance in Experimental Chronic Chagas Cardiomyopathy. J Nucl Med. 2018;59(9):1430-6. doi: 10.2967/jnumed.117.205450.

187. Tanaka DM, Oliveira LFL, Marin-Neto JA, Romano MMD, Carvalho EEV, Barros Filho ACL, et al. Prolonged Dipyridamole Administration Reduces Myocardial Perfusion Defects in Experimental Chronic Chagas Cardiomyopathy. J Nucl Cardiol. 2019;26(5):1569-79. doi: 10.1007/s12350-018-1198-7.

188. Marin-Neto JA, Simões MV, Ayres-Neto EM, Attab-Santos JL, Gallo L Jr, Amorim DS, et al. Studies of the Coronary Circulation in Chagas' Heart Disease. Sao Paulo Med J. 1995;113(2):826-34. doi: 10.1590/s1516-31801995000200014.

189. Torres FW, Acquatella H, Condado JA, Dinsmore R, Palacios IF. Coronary Vascular Reactivity is Abnormal in Patients with Chagas' Heart Disease. Am Heart J. 1995;129(5):995-1001. doi: 10.1016/0002-8703(95)90122-1.

190. Rossi MA. Aortic Endothelial Cell Changes in the Acute Septicemic Phase of Experimental Trypanosoma cruzi Infection in Rats: Scanning and Transmission Electron Microscopic Study. Am J Trop Med Hyg. 1997;57(3):321-7. doi: 10.4269/ajtmh.1997.57.321.

191. Petkova SB, Huang H, Factor SM, Pestell RG, Bouzahzah B, Jelicks LA, et al. The Role of Endothelin in the Pathogenesis of Chagas' Disease. Int J Parasitol. 2001;31(5-6):499-511. doi: 10.1016/s0020-7519(01)00168-0.

192. Köberle F. Chagas' Disease and Chagas' Syndromes: The Pathology of American Trypanosomiasis. Adv Parasitol. 1968;6:63-116. doi: 10.1016/s0065-308x(08)60472-8.

193. Mott KE, Hagstrom JW. The Pathologic Lesions of the Cardiac Autonomic Nervous System in Chronic Chagas' Myocarditis. Circulation. 1965;31:273-86. doi: 10.1161/01.cir.31.2.273.
194. Souza MM, Andrade SG, Barbosa AA Jr, Santos RTM, Alves VA, Andrade ZA. Trypanosoma cruzi Strains and Autonomic Nervous System Pathology in Experimental Chagas Disease. Mem Inst Oswaldo Cruz. 1996;91(2):217-24. doi: 10.1590/s0074-02761996000200018.

195. Machado CR, Caliari MV, Lana M, Tafuri WL. Heart Autonomic Innervation During the Acute Phase of Experimental American trypanosomiasis in the Dog. Am J Trop Med Hyg. 1998;59(3):492-6. doi: 10.4269/ajtmh.1998.59.492.

196. Santos RR, Marquez JO, Von Gal Furtado CC, Oliveira JCR, Martins AR, Köberle F. Antibodies Against Neurons in Chronic Chagas' Disease. Tropenmed Parasitol. 1979;30(1):19-23.

197. Santos R, Hudson L. Denervation and the Immune Response in Mice Infected with Trypanosoma cruzi. Clin Exp Immunol. 1981;44(2):349-54.

198. Amorim DS, Godoy RA, Manço JC, Tanaka A, Gallo L Jr. Effects of Acute Elevation in Blood Pressure and of Atropine on Heart Rate in Chagas' Disease. A preliminary Report. Circulation. 1968;38(2):289-94. doi: 10.1161/01.cir.38.2.289.

199. Gallo L Jr, Marin-Neto JA, Manço JC, Rassi A, Amorim DS. Abnormal Heart Rate Responses During Exercise in Patients with Chagas' Disease. Cardiology. 1975;60(3):147-62. doi: 10.1159/000169713.

200. Guzzetti S, Iosa D, Pecis M, Bonura L, Prosdocimi M, Malliani A. Impaired Heart Rate Variability in Patients with Chronic Chagas' Disease. Am Heart J. 1991;121(6 Pt 1):1727-34. doi: 10.1016/0002-8703(91)90019-e.

201. Marin-Neto JA, Gallo L Jr, Manço JC, Rassi A, Amorim DS. Postural Reflexes in Chronic Chagas's Heart Disease. Heart Rate and Arterial Pressure Responses. Cardiology. 1975;60(6):343-57. doi: 10.1159/000169734.

202. Amorim DS, Manço JC, Gallo L Jr, Marin-Neto JA. Chagas' Heart Disease as an Experimental Model for Studies of Cardiac Autonomic Function in Man. Mayo Clin Proc. 1982;57 Suppl:48-60.

203. Marin-Neto JA, Bromberg-Marin G, Pazin-Filho A, Simões MV, Maciel BC. Cardiac Autonomic Impairment and Early Myocardial Damage Involving the Right Ventricle are Independent Phenomena in Chagas' Disease. Int J Cardiol. 1998;65(3):261-9. doi: 10.1016/s0167-5273(98)00132-6.

204. Ribeiro ALP, Moraes RS, Ribeiro JP, Ferlin EL, Torres RM, Oliveira E, et al. Parasympathetic Dysautonomia Precedes Left Ventricular Systolic Dysfunction in Chagas Disease. Am Heart J. 2001;141(2):260-5. doi: 10.1067/mhj.2001.111406.

205. Barizon GC, Simões MV, Schmidt A, Gadioli LP, Murta LO Jr. Relationship between Microvascular Changes, Autonomic Denervation, and Myocardial Fibrosis in Chagas Cardiomyopathy: Evaluation by MRI and SPECT Imaging. J Nucl Cardiol. 2020;27(2):434-4. doi: 10.1007/s12350-018-1290-z.

206. Landesmann MC, Fonseca LM, Pereira BB, Nascimento EM, Rosado-de-Castro PH, Souza SA, et al. Iodine-123 Metaiodobenzylguanidine Cardiac Imaging as a Method to Detect Early Sympathetic Neuronal Dysfunction in Chagasic Patients with Normal or Borderline Electrocardiogram and Preserved Ventricular Function. Clin Nucl Med. 2011;36(9):757-61. doi: 10.1097/RLU.0b013e31821772a9.

207. Miranda CH, Figueiredo AB, Maciel BC, Marin-Neto JA, Simões MV. Sustained Ventricular Tachycardia is Associated with Regional Myocardial Sympathetic Denervation Assessed with 123I-Metaiodobenzylguanidine in Chronic Chagas Cardiomyopathy. J Nucl Med. 2011;52(4):504-10. doi: 10.2967/jnumed.110.082032.

208. Gadioli LP, Miranda CH, Pintya AO, Figueiredo AB, Schmidt A, Maciel BC, et al. The Severity of Ventricular Arrhythmia Correlates with the Extent of Myocardial Sympathetic Denervation, But Not with Myocardial Fibrosis Extent in Chronic Chagas Cardiomyopathy: Chagas Disease, Denervation and Arrhythmia. J Nucl Cardiol. 2018;25(1):75-83. doi: 10.1007/s12350-016-0556-6.

209. Martín-Escolano J, Marín C, Rosales MJ, Tsaousis AD, Medina-Carmona E, Martín-Escolano R. An Updated View of the *Trypanosoma cruzi* Life Cycle: Intervention Points for an Effective Treatment. ACS Infect Dis. 2022;8(6):1107-15. doi: 10.1021/acsinfecdis.2c00123.

210. Lannes-Vieira J. Trypanosoma cruzi-elicited CD8+ T Cell-Mediated Myocarditis: Chemokine Receptors and Adhesion Molecules as Potential Therapeutic Targets to Control Chronic Inflammation? Mem Inst Oswaldo Cruz. 2003;98(3):299-304. doi: 10.1590/s0074-02762003000300002.

211. Ianni BM, Arteaga E, Frimm CC, Barretto ACP, Mady C. Chagas' Heart Disease: Evolutive Evaluation of Electrocardiographic and Echocardiographic Parameters in Patients with the Indeterminate form. Arq Bras Cardiol. 2001;77(1):59-62. doi: 10.1590/s0066-782x2001000700006.

212. Araujo FG, Chiari E, Dias JC. Demonstration of Trypanosoma cruzi Antigen in Serum from Patients with Chagas' Disease. Lancet. 1981;1(8214):246-9. doi: 10.1016/s0140-6736(81)92088-2.

213. Marinho CR, D'Império Lima MR, Grisotto MG, Alvarez JM. Influence of Acute-Phase Parasite Load on Pathology, Parasitism, and Activation of the Immune System at the late Chronic Phase of Chagas' Disease. Infect Immun. 1999;67(1):308-18. doi: 10.1128/IAI.67.1.308-318.1999.

214. Cunha-Neto E, Coelho V, Guilherme L, Fiorelli A, Stolf N, Kalil J. Autoimmunity in Chagas' Disease. Identification of Cardiac Myosin-B13 Trypanosoma cruzi Protein Crossreactive T Cell Clones in Heart Lesions of a Chronic Chagas' Cardiomyopathy Patient. J Clin Invest. 1996;98(8):1709-12. doi: 10.1172/JCI118969.

215. Bocchi EA, Rassi S, Guimarães GV; Argentina, Chile, and Brazil SHIFT Investigators. Safety Profile and Efficacy of Ivabradine in Heart Failure due to Chagas Heart Disease: A Post hoc Analysis of the SHIFT Trial. ESC Heart Fail. 2018;5(3):249-56. doi: 10.1002/ehf2.12240.

216. Barretto AC, Higuchi ML, Luz PL, Lopes EA, Bellotti G, Mady C, et al. Comparison of Histologic Changes in Chagas' Cardiomyopathy and Dilated Cardiomyopathy. Arq Bras Cardiol. 1989;52(2):79-83.

217. Jones EM, Colley DG, Tostes S, Lopes ER, Vnencak-Jones CL, McCurley TL. Amplification of a Trypanosoma cruzi DNA Sequence from Inflammatory Lesions in Human Chagasic Cardiomyopathy. Am J Trop Med Hyg. 1993;48(3):348-57. doi: 10.4269/ajtmh.1993.48.348.

218. Abel LC, Kalil J, Cunha Neto E. Molecular Mimicry between Cardiac Myosin and Trypanosoma cruzi Antigen B13: Identification of a B13-Driven Human T Cell Clone that Recognizes Cardiac Myosin. Braz J Med Biol Res. 1997;30(11):1305-8. doi: 10.1590/s0100-879x1997001100007.

219. Neves EGA, Koh CC, Souza-Silva TG, Passos LSA, Silva ACC, Velikkakam T, et al. T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies. Front Cardiovasc Med. 2022;9:787423. doi: 10.3389/fcvm.2022.787423.

220. Kroll-Palhares K, Silvério JC, Silva AA, Michailowsky V, Marino AP, Silva NM, et al. TNF/TNFR1 Signaling Up-Regulates CCR5 Expression by CD8+ T Lymphocytes and Promotes Heart Tissue Damage During Trypanosoma cruzi Infection: Beneficial Effects of TNF-Alpha Blockade. Mem Inst Oswaldo Cruz. 2008;103(4):375-85. doi: 10.1590/s0074-02762008000400011.

221. James TN, Rossi MA, Yamamoto S. Postmortem Studies of the Intertruncal Plexus and Cardiac Conduction System from Patients with Chagas Disease who Died Suddenly. Prog Cardiovasc Dis. 2005;47(4):258-75. doi: 10.1016/j.pcad.2005.01.003.

222. Machado CR, Camargos ER, Guerra LB, Moreira MC. Cardiac Autonomic Denervation in Congestive Heart Failure: Comparison of Chagas' Heart Disease with Other Dilated Cardiomyopathy. Hum Pathol. 2000;31(1):3-10. doi: 10.1016/s0046-8177(00)80191-4.

223. Koeberle F. Cardiopathia Parasympathicopriga. Munch Med Wochenschr. 1959;101:1308-10.

224. Chapadeiro E, Lopes ER, Pereira FE. Parasympathetic Denervation and Myocardial Hypertrophy in Chronic Chagas' Disease. Rev Inst Med Trop Sao Paulo. 1967;9(1):40-2.

225. Machado AB, Machado CR, Gomez MV. Trypanosoma cruzi: Acetylcholine Content and Cholinergic Innervation of the Heart in Rats. Exp Parasitol. 1979;47(1):107-15. doi: 10.1016/0014-4894(79)90012-2.
226. Machado CR, Ribeiro ALP. Experimental American Trypanomiasis in Rats: Sympathetic Denervation, Parasitism and Inflammatory Process. Mem Inst Oswaldo Cruz. 1989;84(4):549-56. doi: 10.1590/s0074-02761989000400013.

227. Machado CR, Machado AB, Chiari CA. Recovery from Heart Norepinephrine Depletion in Experimental Chagas' Disease. Am J Trop Med Hyg. 1978;27(1 Pt 1):20-4. doi: 10.4269/ajtmh.1978.27.20.

228. Camargos ER, Machado CR. Morphometric and Histological Analysis of the Superior Cervical Ganglion in Experimental Chagas' Disease in Rats. Am J Trop Med Hyg. 1988;39(5):456-62. doi: 10.4269/ajtmh.1988.39.456.

229. Chagas C. Processos Patojenicos da Tripanozomiase Americana. Mem Inst Oswaldo Cruz. 1916;8(2):5-36. doi: 10.1590/S0074-02761916000200002.

230. Böhm GM. Quantitative Study of the Intrinsic Innervation of the Heart in Endomyocardial Fibrosis and African Idiopathic Cardiopathies. Rev Inst Med Trop Sao Paulo. 1968;10(2):84-7.

231. Amorim DS, Olsen EG. Assessment of Heart Neurons in Dilated (Congestive) Cardiomyopathy. Br Heart J. 1982;47(1):11-8. doi: 10.1136/hrt.47.1.11.

232. Medei EH, Nascimento JH, Pedrosa RC, Carvalho AC. Role of Autoantibodies in the Physiopathology of Chagas' Disease. Arq Bras Cardiol. 2008;91(4):257-62, 281-6. doi: 10.1590/S0066-782x2008001600012.

233. Rodriguez HO. Histopathological Analysis of the Pro-arrhythmogenic Changes in a Suspected Chagas Disease Sudden Death. Heart Res Open J. 2020;7(1):11-6. doi: 10.17140/HROJ-7-155.

234. Schwaiger M, Kalf V, Rosenspire K, Haka MS, Molina E, Hutchins GD, et al. Noninvasive Evaluation of Sympathetic Nervous System in Human Heart by Positron Emission Tomography. Circulation. 1990;82(2):457-64. doi: 10.1161/01.cir.82.2.457.

235. Fonseca LMB, Xavier SS, Castro PHR, Lima RS, Gutfilen B, Goldenberg RC, et al. Biodistribution of Bone Marrow Mononuclear Cells in Chronic Chagasic Cardiomyopathy after Intracoronary Injection. Int J Cardiol. 2011;149(3):310-4. doi: 10.1016/j.ijcard.2010.02.008.

236. Marin-Neto JA, Gallo L Jr, Manco JC, Rassi A, Amorim DS. Mechanisms of Tachycardia on Standing: Studies in Normal Individuals and in Chronic Chagas' Heart Patients. Cardiovasc Res. 1980;14(9):541-50. doi: 10.1093/cvr/14.9.541.

237. Machado MPR, Silva VJD. Autonomic Neuroimmunomodulation in Chagasic Cardiomyopathy. Exp Physiol. 2012;97(11):1151-60. doi: 10.1113/exphysiol.2012.066381.

238. Owen N, Steptoe A. Natural Killer Cell and Proinflammatory Cytokine Responses to Mental Stress: Associations with Heart Rate and Heart Rate Variability. Biol Psychol. 2003;63(2):101-15. doi: 10.1016/S0301-0511(03)00023-1.

239. Strom TB, Deisseroth A, Morganroth J, Carpenter CB, Merrill JP. Alteration of the Cytotoxic Action of Sensitized Lymphocytes by Cholinergic Agents and Activators of Adenylate Cyclase. Proc Natl Acad Sci USA. 1972;69(10):2995-9. doi: 10.1073/pnas.69.10.2995.

240. Blalock JE. The Immune System as the Sixth Sense. J Intern Med. 2005;257(2):126-38. doi: 10.1111/j.1365-2796.2004.01441.x.

241. Oliveira SF, Pedrosa RC, Nascimento JH, Carvalho ACC, Masuda MO. Sera from Chronic Chagasic Patients with Complex Cardiac Arrhythmias Depress Electrogenesis and Conduction in Isolated Rabbit Hearts. Circulation. 1997;96(6):2031-7. doi: 10.1161/01.cir.96.6.2031.

242. Masuda MO, Levin M, Oliveira SF, Costa PCS, Bergami PL, Almeida NAS, et al. Functionally Active Cardiac Antibodies in Chronic Chagas' Disease are Specifically Blocked by Trypanosoma cruzi Antigens. FASEB J. 1998;12(14):1551-8. doi: 10.1096/fasebj.12.14.1551.

243. Cunha-Neto E, Bilate AM, Hyland KV, Fonseca SG, Kalil J, Engman DM. Induction of Cardiac Autoimmunity in Chagas Heart Disease: A Case for Molecular Mimicry. Autoimmunity. 2006;39(1):41-54. doi: 10.1080/08916930500485002.

244. Thiers CA, Barbosa JL, Pereira BB, Nascimento EM, Nascimento JH, Medei EH, et al. Autonomic Dysfunction and anti-M2 and anti-β1 Receptor Antibodies in Chagas Disease Patients. Arq Bras Cardiol. 2012;99(2):732-9. doi: 10.1590/S0066-782x2012005000067.

245. Pedrosa RC. Dysautonomic Arrhythmogenesis: A Working Hypothesis in Chronic Chagas Cardiomyopathy. Int J Cardiovasc Sci. 2020;33(6):713-20. doi: 10.3666/ijcs.202002196.

246. Beltrame SP, Páez LCC, Auger SR, Sabra AH, Bilder CR, Waldner CI, et al. Impairment of Agonist-Induced M, Muscarinic Receptor Activation by Autoantibodies from Chagasic Patients with Cardiovascular Dysautonomia. Clin Immunol. 2020;212:108346. doi: 10.1016/j.clim.2020.108346.

247. Zingales B, Miles MA, Campbell DA, Tibayrenc M, Macedo AM, Teixeira MM, et al. The Revised Trypanosoma cruzi Subspecific Nomenclature: Rationale, Epidemiological Relevance and Research Applications. Infect Genet Evol. 2012;12(2):240-53. doi: 10.1016/j.meegid.2011.12.009.

248. Zingales B, Miles MA, Campbell DA, Tibayrenc M, Macedo AM, Teixeira MM, et al. The Revised Trypanosoma cruzi Subspecific Nomenclature: Rationale, Epidemiological Relevance and Research Applications. Infect Genet Evol. 2012;12(2):240-53. doi: 10.1016/j.meegid.2011.12.009.

249. Vela A, Coral-Almeida M, Sereno D, Costales JA, Barnabé C, Brenière SF. In Vitro Susceptibility of Trypanosoma cruzi Discrete Typing Units (DTUs) to Benznidazole: A Systematic Review and Meta-Analysis. PLoS Negl Trop Dis. 2021;15(3):e0009269. doi: 10.1371/journal.pntd.0009269.

250. Zingales B. Trypanosoma cruzi Genetic Diversity: Something New for Something Known about Chagas Disease Manifestations, Serodiagnosis and Drug Sensitivity. Acta Trop. 2018;184:38-52. doi: 10.1016/j.actatropica.2017.09.017.

251. Zingales B, Bartholomeu DC. Trypanosoma cruzi Genetic Diversity: Impact on Transmission Cycles and Chagas Disease. Mem Inst Oswaldo Cruz. 2022;117:e210193. doi: 10.1590/0074-02760210193.

252. Casanova JL, Abel L. The Human Model: A Genetic Dissection of Immunity to Infection in Natural Conditions. Nat Rev Immunol. 2004;4(1):55-66. doi: 10.1038/nri1264.

253. Batista AM, Alvarado-Arnez LE, Alves SM, Melo G, Pereira IR, Ruivo LAS, et al. Genetic Polymorphism at CCL5 Is Associated with Protection in Chagas' Heart Disease: Antagonistic Participation of CCR1⁺ and CCR5⁺ Cells in Chronic Chagasic Cardiomyopathy. Front Immunol. 2018;9:615. doi: 10.3389/fimmu.2018.00615.

254. Drigo SA, Cunha-Neto E, Ianni B, Cardoso MR, Braga PE, Faé KC, et al. TNF Gene Polymorphisms are Associated with Reduced Survival in Severe Chagas' Disease Cardiomyopathy Patients. Microbes Infect. 2006;8(3):598-603. doi: 10.1016/j.micinf.2005.08.009.

255. Drigo SA, Cunha-Neto E, Ianni B, Mady C, Faé KC, Buck P, et al. Lack of Association of Tumor Necrosis Factor-Alpha Polymorphisms with Chagas Disease in Brazilian Patients. Immunol Lett. 2007;108(1):109-11. doi: 10.1016/j.imlet.2006.10.008.

256. Beraún Y, Nieto A, Collado MD, González A, Martín J. Polymorphisms at Tumor Necrosis Factor (TNF) Loci are Not Associated with Chagas' Disease. Tissue Antigens. 1998;52(1):81-3. doi: 10.1111/j.1399-0039.1998.tb03028.x.

257. Albuquerque FN, Brandão AA, Silva DA, Mourilhe-Rocha R, Duque GS, Gondar AF, et al. Angiotensin-Converting Enzyme Genetic Polymorphism: Its Impact on Cardiac Remodeling. Arq Bras Cardiol. 2014;102(1):70-9. doi: 10.5935/abc.20130229.

258. Andersson B, Sylvén C. The DD Genotype of the Angiotensin-Converting Enzyme Gene is Associated with Increased Mortality in Idiopathic Heart Failure. J Am Coll Cardiol. 1996;28(1):162-7. doi: 10.1016/0735-1097(96)00098-8.

259. Pascuzzo-Lima C, Mendible JC, Bonfante-Cabarcas RA. Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphism and Progression of Chagas' Cardiomyopathy. Rev Esp Cardiol. 2009;62(3):320-2. doi: 10.1016/S1885-5857(09)71564-6.
260. Silva SJD, Rassi S, Pereira ADC. Angiotensin-Converting Enzyme ID Polymorphism in Patients with Heart Failure Secondary to Chagas Disease. Arq Bras Cardiol. 2017;109(4):307-312. doi: 10.5935/abc.20170137.

261. Alves SMM, Alvarado-Arnês LE, Cavalcanti MDGAM, Carrazzone CFV, Pacheco AGF, Sarteschi C, et al. Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease. Rev Soc Bras Med Trop. 2020;53:e20190488. doi: 10.1590/0037-8682-0488-2019.

262. Sayed-Tabatabaei FA, Schut AF, Hofman A, Bertoli-Avella AM, Vergeer J, Witteman JC, et al. A Study of Gene--Environment Interaction on the Gene for Angiotensin Converting Enzyme: A Combined Functional and Population Based Approach. J Med Genet. 2004;41(2):99-103. doi: 10.1136/jmg.2003.013441.

263. Poncini CV, Benatar AF, Gomez KA, Rabinovich GA. Galectins in Chagas Disease: A Missing Link Between Trypanosoma cruzi Infection, Inflammation, and Tissue Damage. Front Microbiol. 2022;12:794765. doi: 10.3389/fmicb.2021.794765.

264. Higuchi ML, Kawakami J, Ikegami R, Clementino MB, Kawamoto FM, Reis MM, et al. Do Archaea and Bacteria Co-Infection Have a Role in the Pathogenesis of Chronic Chagasic Cardiopathy? Mem Inst Oswaldo Cruz. 2009;104 Suppl 1:199-207. doi: 10.1590/s0074-02762009000900026.

265. Higuchi ML, Kawakami JT, Ikegami RN, Reis MM, Pereira JJ, Ianni BM, et al. Archaea Symbiont of *T. cruzi* Infection May Explain Heart Failure in Chagas Disease. Front Cell Infect Microbiol. 2018;8:412. doi: 10.3389/fcimb.2018.00412.

266. Andrade ZA, Silva HR. Parasitism of Adipocytes by Trypanosoma cruzi. Mem Inst Oswaldo Cruz. 1995;90(4):521-2. doi: 10.1590/s0074-02761995000400018.

267. Combs TP, Nagajyothi, Mukherjee S, Almeida CJ, Jelicks LA, Schubert W, et al. The Adipocyte as an Important Target Cell for Trypanosoma cruzi Infection. J Biol Chem. 2005;280(25):24085-94. doi: 10.1074/jbc.M412802200.

268. Nagajyothi F, Desruisseaux MS, Machado FS, Upadhya R, Zhao D, Schwartz GJ, et al. Response of Adipose Tissue to Early Infection with Trypanosoma cruzi (Brazil strain). J Infect Dis. 2012;205(5):830-40. doi: 10.1093/infdis/jir840.

269. Cardoso S, Azevedo Filho CF, Fernandes F, Ianni B, Torreão JA, Marques MD, et al. Lower Prevalence and Severity of Coronary Atherosclerosis in Chronic Chagas' Disease by Coronary Computed Tomography Angiography. Arq Bras Cardiol. 2020;115(6):1051-60. doi: 10.36660/abc.20200342.

270. Higuchi ML, Benvenuti LA, Reis MM, Metzger M. Pathophysiology of the Heart in Chagas' Disease: Current Status and New Developments. Cardiovasc Res. 2003;60(1):96-107. doi: 10.1016/s0008-6363(03)00361-4.

271. Chaves AT, Menezes CAS, Costa HS, Nunes MCP, Rocha MOC. Myocardial Fibrosis in Chagas Disease and Molecules Related to Fibrosis. Parasite Immunol. 2019;41(10):e12663. doi: 10.1111/pim.12663.

272. Waghabi MC, Ferreira RR, Abreu RDS, Degrave W, Souza EM, Bailly S, et al. Transforming Growth Factor-β as a Therapeutic Target for the Cardiac Damage of Chagas Disease. Mem Inst Oswaldo Cruz. 2022;117:e210395. doi: 10.1590/0074-02760210395.

273. Passos LSA, Koh CC, Magalhães LMD, Nunes MDCP, Gollob KJ, Dutra WO. Distinct CD4-CD8 (Double-Negative) Memory T-Cell Subpopulations Are Associated with Indeterminate and Cardiac Clinical forms of Chagas Disease. Front Immunol. 2021;12:761795. doi: 10.3389/fimmu.2021.761795.

274. Lannes-Vieira J. Multi-Therapeutic Strategy Targeting Parasite and Inflammation-Related Alterations to Improve Prognosis of Chronic Chagas Cardiomyopathy: A Hypothesis-Based Approach. Mem Inst Oswaldo Cruz. 2022;117:e220019. doi: 10.1590/0074-02760220019.

275. Imperador CHL, Scarim CB, Bosques PL, Lopes JR, Cardinalli Neto A, Giarolla J, et al. Resveratrol and Curcumin for Chagas Disease Treatment-A Systematic Review. Pharmaceuticals. 2022;15(5):609. doi: 10.3390/ph15050609.

276. Macedo CT, Larocca TF, Noya-Rabelo M, Aras R Jr, Macedo CRB, Moreira MI, et al. Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial. Front Cardiovasc Med. 2022;9:864837. doi: 10.3389/fcvm.2022.864837.

277. Grijalva A, Vaulet LG, Agüero RN, Toledano A, Risso MG, Braghini JQ, et al. Interleukin 10 Polymorphisms as Risk Factors for Progression to Chagas Disease Cardiomyopathy: A Case-Control Study and Meta-Analysis. Front Immunol. 2022;13:946350. doi: 10.3389/fimmu.2022.946350.

278. Camandaroba EL, Lima CMP, Andrade SG. Oral Transmission of Chagas Disease: Importance of Trypanosoma cruzi Biodeme in the Intragastric Experimental Infection. Rev Inst Med Trop Sao Paulo. 2002;44(2):97-103. doi: 10.1590/s0036-46652002000200008.

279. Pinto AY, Valente SA, Valente VC, Ferreira AG Jr, Coura JR. Acute Phase of Chagas Disease in the Brazilian Amazon Region: Study of 233 Cases from Pará, Amapá and Maranhão Observed between 1988 and 2005. Rev Soc Bras Med Trop. 2008;41(6):602-14. doi: 10.1590/s0037-86822008000600011.

280. Marques J, Mendoza I, Noya B, Acquatella H, Palacios I, Marques-Mejias M. ECG Manifestations of the Biggest Outbreak of Chagas Disease due to Oral Infection in Latin-America. Arq Bras Cardiol. 2013;101(3):249-54. doi: 10.5935/abc.20130144.

281. Sanches TL, Cunha LD, Silva GK, Guedes PM, Silva JS, Zamboni DS. The Use of a Heterogeneously Controlled Mouse Population Reveals a Significant Correlation of Acute Phase Parasitemia with Mortality in Chagas Disease. PLoS One. 2014;9(3):e91640. doi: 10.1371/journal.pone.0091640.

282. Prado CM, Jelicks LA, Weiss LM, Factor SM, Tanowitz HB, Rossi MA. The Vasculature in Chagas Disease. Adv Parasitol. 2011;76:83-99. doi: 10.1016/B978-0-12-385895-5.00004-9.

283. Souza DS, Araujo MT, Santos PRSG, Furtado JC, Figueiredo MT, Povoa RM. Anatomopathological Aspects of Acute Chagas Myocarditis by Oral Transmission. Arq Bras Cardiol. 2016;107(1):77-80. doi: 10.5935/abc.20160110.

284. Miziara HL, Santos BG, Lopes ER, Tafuri WR, Chapadeiro E. Contribuição ao Conhecimento do Quadro Anatomopatológico do Coração na Doença de Chagas. Rev Soc Bras Med Trop. 1984;17:101-5. doi: 10.1590/S0037-86821984000200010.

285. Torres CM, Duarte E. Miocardite na Forma Aguda da Doença de Chagas. Mem. Inst Oswaldo Cruz. 1948-1949;46(4):759-93. doi: 10.1590/S0074-02761948000400006.

286. Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet. 2012;379(9817):738-47. doi: 10.1016/S0140-6736(11)60648-X.

287. Custodio LC, Moraes JC, Dantas AL, Figueiredo MTS, Póvoa R, Bianco HT et al. Perfil Clínico Hemodinâmico da Insuficiência Cardíaca na Doença de Chagas Aguda. In: 28th Congresso Brasileiro De Insuficiência Cardíaca Aguda; 2019. Fortaleza: DEIC; 2019, p. 7-60.

288. Souza DSM, Almeida AJB, Costa FA, de Goes E, Figueiredo MTS, Póvoa RMS. O Eletrocardiograma na Fase Aguda da Doença de Chagas por Transmissão Oral. Rev Bras Cardiol. 2013;26(2):127-30.

289. Barbosa-Ferreira JM, Guerra JA, Santana Filho FS, Magalhães BM, Coelho LI, Barbosa M. Cardiac Involvement in Acute Chagas' Disease Cases in the Amazon Region. Arq Bras Cardiol. 2010;94(6):147-9. doi: 10.1590/s0066-782x2010000600023.

290. Vazquez BP, Vazquez TP, Miguel CB, Rodrigues WF, Mendes MT, Oliveira CJ, et al. Inflammatory Responses and Intestinal Injury Development During Acute Trypanosoma cruzi Infection are Associated with the Parasite Load. Parasit Vectors. 2015;8:206. doi: 10.1186/s13071-015-0811-8.
291. Pinto AYDN, Valente VDC, Valente SADS, Motta TAR, Ventura AMRDS. Clinical, Cardiological and Serologic Follow-Up of Chagas Disease in Children and Adolescents from the Amazon Region, Brazil: Longitudinal Study. Trop Med Infect Dis. 2020;5(3):139. doi: 10.3390/ tropicalmed5030139.

292. Rassi A. Clínica: Fase Aguda. In: Brenner Z, Andrade Z, editors. Trypanosoma cruzi e Doença de Chagas. Rio de Janeiro: Guanabara Koogan; 1979.

293. Dias JCP. Revisão Geral e Evolução Imediata de Casos Agudos de Doença de Chagas Estudados No Posto Avançado Emmanuel Dias (Bambuí, MG, Brasil) entre 1940 e 1969. Rev Med Minas Gerais. 2009;19(4):325-35.

294. Souza DM, Povoa RMS. Aspectos Epidemiológicos e Clínicos da Doença de Chagas Aguda no Brasil e na América Latina. Rev Soc Cardiol do Estado de São Paulo. 2016;26(4):222-9.

295. Dias JCP. Doença de Chagas em Bambuí, Minas Gerais, Brasil: Estudo Clínico-epidemiológico a Partir da Fase Aguda, entre 1940 e 1982 [dissertation]. Belo Horizonte: Universidade Federal de Minas Gerais; 1982.

296. Dias JCP. Etiopatogenia e História Natural da Doença de Chagas Humana. Rev Patol Trop. 1985;14(1):17-29. doi: 10.5216/rpt.v14i1.21258.

297. Chadalawada S, Sillau S, Archuleta S, Mundo W, Bandali M, Parra-Henao G, et al. Risk of Chronic Cardiomyopathy Among Patients with the Acute Phase or Indeterminate form of Chagas Disease: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(8):e2015072. doi: 10.1001/ jamanetworkopen.2020.15072.

298. Montera MW, Mesquita ET, Colafranceschi AS, Oliveira AM Jr, Rabischoffsky A, Ianni BM, et al. I Diretriz Brasileira de Miocardites e Pericardites. Arq Bras Cardiol. 2013;100(4):1-36. doi: 10.5935/abc.2013S004.

299. Ribeiro ALP, Rocha MO. Indeterminate form of Chagas Disease: Considerations about Diagnosis and Prognosis. Rev Soc Bras Med Trop. 1998;31(3):301-14. doi: 10.1590/s0037-86821998000300008.

300. Dias JC. The Indeterminate form of Human Chronic Chagas' Disease: A Clinical Epidemiological Review. Rev Soc Bras Med Trop. 1989;22(3):147-56. doi: 10.1590/s0037-86821989000300007.

301. I Reunião de Pesquisa Aplicada em doença de Chagas: Validade do conceito de forma indeterminada. Rev Soc Bras Med Trop. 1985;18:46.

302. Sabino EC, Ribeiro ALP, Salemi VM, Oliveira CDO, Antunes AP, Menezes MM, et al. Ten-year Incidence of Chagas Cardiomyopathy Among Asymptomatic Trypanosoma cruzi-Seropositive former Blood Donors. Circulation. 2013;127(10):1105-15. doi: 10.1161/CIRCULATIONAHA.112.123612.

303. Ribeiro ALP, Marcolino MS, Primeas RJ, Lima-Costa MF. Electrocardiographic Abnormalities in Elderly Chagas Disease Patients: 10-Year Follow-Up of the Bambui Cohort Study of Aging. J Am Heart Assoc. 2014;3(1):e000632. doi: 10.1161/JAHA.113.000632.

304. Chagas C, Villela E. Forma Cardíaca da Trypanosomiase Americana. Mem Inst Oswaldo Cruz. 1922;14(1):5-61.

305. Dias E, Laranja FS, Miranda A, Nobrega G. Chagas' Disease: a Clinical, Epidemiologic, and Pathologic Study. Circulation. 1956;14(6):1035-60. doi: 10.1161/01.cir.14.6.1035.

306. Marin-Neto JA, Almeida Filho OC, Pazin-Filho A, Maciel BC. Indeterminate form of Chagas' Disease. Proposal of New Diagnostic Criteria and Perspectives for Early Treatment of Cardiomyopathy. Arq Bras Cardiol. 2002;79(6):623-7. doi: 10.1590/s0066-782x2002001500008.

307. Barretto AC, Azul LG, Mady C, Ianni BM, Vianna CB, Belloti G, et al. Indeterminate form of Chagas' Disease. A Polymorphic Disease. Arq Bras Cardiol. 1990;55(6):347-53.

308. Ortiz J, Barretto AC, Matsumoto AY, Mônaco CA, Ianni B, Marotta RH, et al. Segmental Contractility Changes in the Indeterminate form of Chagas' Disease. Echocardiographic Study. Arq Bras Cardiol. 1987;49(4):217-20.

309. Mady C, Pereira-Barretto AC, Ianni BM, Lopes EA, Pleggi F. Right Ventricular Endomyocardial Biopsy in Undetermined form of Chagas' Disease. Angiology. 1984;35(12):755-9. doi: 10.1177/000331978403501201.

310. Torreão JA, Ianni BM, Mady C, Naia E, Rassi CH, Nomura C, et al. Myocardial Tissue Characterization in Chagas' Heart Disease by Cardiovascular Magnetic Resonance. J Cardiovasc Magn Reson. 2015;17:97. doi: 10.1186/ s12968-015-0200-7.

311. Rochitte CE, Oliveira PF, Andrade JM, Ianni BM, Parga JR, Avila LF, et al. Myocardial Delayed Enhancement by Magnetic Resonance Imaging in Patients with Chagas' Disease: A Marker of Disease Severity. J Am Coll Cardiol. 2005;46(8):1553-8. doi: 10.1016/j.jacc.2005.06.067.

312. Barros MV, Rocha MO, Ribeiro ALP, Machado FS. Doppler Tissue Imaging to Evaluate Early Myocardium Damage in Patients with Undetermined form of Chagas' Disease and Normal Echocardiogram. Echocardiography. 2001;18(2):131-6. doi: 10.1046/j.1540-8175.2001.00131.x.

313. Barbosa MM, Rocha MOC, Vidigal DF, Carneiro RBC, Araújo RD, Palma MC, et al. Early Detection of Left Ventricular Contractility Abnormalities by Two-Dimensional Speckle Tracking Strain in Chagas' Disease. Echocardiography. 2014;31(5):623-30. doi: 10.1111/echo.12426.

314. Zhang L, Tarleton RL. Parasite Persistence Correlates with Disease Severity and Localization in Chronic Chagas' Disease. J Infect Dis. 1999;180(2):480-6. doi: 10.1086/314889.

315. Schijman AG, Vigliano CA, Viotti RJ, Burgos JM, Brandariz S, Lococo BE, et al. Trypanosoma cruzi DNA in Cardiac Lesions of Argentinean Patients with End-Stage Chronic Chagas Heart Disease. Am J Trop Med Hyg. 2004;70(2):210-20.

316. Benvenuti LA, Roggério A, Freitas HF, Mansur AJ, Fiorelli A, Higuchi ML. Chronic American trypanosomiasis: Parasite Persistence in Endomyocardial Biopsies is Associated with High-Grade Myocarditis. Ann Trop Med Parasitol. 2008;102(6):481-7. doi: 10.1179/136485908X311740.

317. Sabino EC, Ribeiro ALP, Lee TH, Oliveira CL, Carneiro-Proieta AB, Antunes AP, et al. Detection of Trypanosoma cruzi DNA in blood by PCR is Associated with Chagas Cardiomyopathy and Disease Severity. Eur J Heart Fail. 2015;17(4):416-23. doi: 10.1002/ejhf.220.

318. Cardoso CS, Ribeiro ALP, Oliveira CDL, Oliveira LC, Ferreira AM, Bierrenbach AL, et al. Beneficial Effects of Benznidazole in Chagas Disease: NIH SaMi-Trop Cohort Study. PLoS Negl Trop Dis. 2018;12(11):e0006814. doi: 10.1371/journal.pntd.0006814.

319. Nunes MCP, Buss LF, Silva JLP, Martins LNA, Oliveira CDL, Cardoso CS, et al. Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals. Circulation. 2021;144(19):1553-66. doi: 10.1161/ CIRCULATIONAHA.121.055112.

320. Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, et al. Long-Term Cardiac Outcomes of Treating Chronic Chagas Disease with Benznidazole versus no Treatment: A Nonrandomized Trial. Ann Intern Med. 2006;144(10):724-34. doi: 10.7326/0003-4819-144-10- 200605160-00006.

321. Fabbro DL, Streiger ML, Arias ED, Bizai ML, del Barco M, Amicone NA. Trypanocide Treatment Among Adults with Chronic Chagas Disease Living in Santa Fe City (Argentina), Over a Mean Follow-Up of 21 Years: Parasitological, Serological and Clinical Evolution. Rev Soc Bras Med Trop. 2007;40(1):1-10. doi: 10.1590/s0037-86822007000100001.

322. Fragata-Filho AA, França FF, Fragata CS, Lourenço AM, Faccini CC, Costa CA. Evaluation of Parasiticide Treatment with Benznidazol in the Electrocardiographic, Clinical, and Serological Evolution of Chagas Disease. PLoS Negl Trop Dis. 2016;10(3):e0004508. doi: 10.1371/journal. pntd.0004508.

323. Hasslocher-Moreno AM, Saraiva RM, Sangenis LHC, Xavier SS, Sousa AS, Costa AR, et al. Benznidazole Decreases the Risk of Chronic Chagas Disease Progression and Cardiovascular Events: A Long-Term Follow Up Study. EClinicalMedicine. 2020;31:100694. doi: 10.1016/j.eclinm.2020.100694.

324. Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A Jr, Rosas F, et al. Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy. N Engl J Med. 2015;373(14):1295-306. doi: 10.1056/ NEJMoa1507574.
325. Rassi A Jr, Marin-Neto JA, Rassi A. Chronic Chagas Cardiomyopathy: A Review of the Main Pathogenic Mechanisms and the Efficacy of Aetiological Treatment Following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial. Mem Inst Oswaldo Cruz. 2017;112(3):224-35. doi: 10.1590/0074-02760160334.

326. Ribeiro ALP, Nunes MP, Teixeira MM, Rocha MO. Diagnosis and Management of Chagas Disease and Cardiomyopathy. Nat Rev Cardiol. 2012;9(10):576-89. doi: 10.1038/nrcardio.2012.109.

327. Rosenbaum MB, Alvarez AJ. The Electrocardiogram in Chronic Chagasic Myocarditis. Am Heart J. 1955;50(4):492-527. doi: 10.1016/0002-8703(55)90296-9.

328. Brito BOF, Ribeiro ALP. Electrocardiogram in Chagas Disease. Rev Soc Bras Med Trop. 2018;51(5):570-77. doi: 10.1590/0037-8682-0184-2018.

329. Maguire JH, Mott KE, Lehman JS, Hoff R, Muniz TM, Guimarães AC, et al. Relationship of Electrocardiographic Abnormalities and Seropositivity to Trypanosoma cruzi Within a Rural Community in Northeast Brazil. Am Heart J. 1983;105(2):287-94. doi: 10.1016/0002-8703(83)90529-8.

330. Marcolino MS, Palhares DM, Ferreira LR, Ribeiro ALP. Electrocardiogram and Chagas Disease: A Large Population Database of Primary Care Patients. Glob Heart. 2015;10(3):167-72. doi: 10.1016/j.gheart.2015.07.001.

331. Ribeiro ALP, Rocha MO, Barros MV, Rodrigues AR, Machado FS. A Narrow QRS Does Not Predict a Normal Left Ventricular Function in Chagas' Disease. Pacing Clin Electrophysiol. 2000;23(11 Pt 2):2014-7. doi: 10.1111/j.1540-8159.2000.tb07076.x.

332. Ribeiro ALP, Sabino EC, Marcolino MS, Salemi VM, Ianni BM, Fernandes F, et al. Electrocardiographic Abnormalities in Trypanosoma cruzi Seropositive and Seronegative Former Blood Donors. PLoS Negl Trop Dis. 2013;7(2):e2078. doi: 10.1371/journal.pntd.0002078.

333. Barretto AC, Bellotti G, Deperon SD, Arteaga-Fernández E, Mady C, Ianni BM, et al. The Value of the Electrocardiogram in Evaluating Myocardial Function in Patients with Chagas' Disease. Arq Bras Cardiol. 1989;52(2):69-73.

334. Casado J, Davila DF, Donis JH, Torres A, Payares A, Colmenares R, et al. Electrocardiographic Abnormalities and Left Ventricular Systolic Function in Chagas' Heart Disease. Int J Cardiol. 1990;27(1):55-62. doi: 10.1016/0167-5273(90)90191-7.

335. Perez AA, Ribeiro ALP, Barros MV, Sousa MR, Bittencourt RJ, Machado FS, et al. Value of the Radiological Study of the Thorax for Diagnosing Left Ventricular Dysfunction in Chagas' disease. Arq Bras Cardiol. 2003;80(2):208-13. doi: 10.1590/s0066-782x2003000200009.

336. Marin-Neto JA, Romano MMD, Maciel BC, Simões MV, Schmidt A. Cardiac Imaging in Latin America: Chagas Heart Disease. Curr Cardiovasc Imaging Rep. 2015;8(4):1-15. doi: 10.1007/s12410-015-9324-2.

337. Ramos MRF, Moreira HT, Volpe GJ, Romano M, Maciel BC, Schmidt A, et al. Correlation between Cardiomegaly on Chest X-Ray and Left Ventricular Diameter on Echocardiography in Patients with Chagas Disease. Arq Bras Cardiol. 2021;116(1):68-74. doi: 10.36660/abc.20190673.

338. Barral MM, Nunes MC, Barbosa MM, Ferreira CS, Tavares WC Jr, Rocha MO. Echocardiographic Parameters Associated with Pulmonary Congestion in Chagas cardiomyopathy. Rev Soc Bras Med Trop. 2010;43(3):244-8. doi: 10.1590/S0037-86822010000300006.

339. Acquatella H. Echocardiography in Chagas heart Disease. Circulation. 2007;115(9):1124-31. doi: 10.1161/CIRCULATIONAHA.106.627323.

340. Viotti RJ, Vigliano C, Laucella S, Lococo B, Petti M, Bertocchi G, et al. Value of Echocardiography for Diagnosis and Prognosis of Chronic Chagas Disease Cardiomyopathy Without Heart Failure. Heart. 2004;90(6):655-60. doi: 10.1136/hrt.2003.018960.

341. Pazin-Filho A, Romano MM, Almeida-Filho OC, Furuta MS, Viviani LF, Schmidt A, et al. Minor Segmental Wall Motion Abnormalities Detected in Patients with Chagas' Disease Have Adverse Prognostic Implications. Braz J Med Biol Res. 2006;39(4):483-7. doi: 10.1590/s0100-879x2006000400008.

342. Schmidt A, Romano MMD, Marin-Neto JA, Rao-Melacini P, Rassi A Jr, Mattos A, et al. Effects of Trypanocidal Treatment on Echocardiographic Parameters in Chagas Cardiomyopathy and Prognostic Value of Wall Motion Score Index: A BENEFIT Trial Echocardiographic Substudy. J Am Soc Echocardiogr. 2019;32(2):286-295.e3. doi: 10.1016/j.echo.2018.09.006.

343. Nunes MC, Barbosa MM, Brum VA, Rocha MO. Morphofunctional Characteristics of the Right Ventricle in Chagas' Dilated Cardiomyopathy. Int J Cardiol. 2004;94(1):79-85. doi: 10.1016/j.ijcard.2003.05.003.

344. Barros MV, Machado FS, Ribeiro ALP, Rocha MOC. Detection of Early Right Ventricular Dysfunction in Chagas' Disease Using Doppler Tissue Imaging. J Am Soc Echocardiogr. 2002;15(10 Pt 2):1197-201. doi: 10.1067/mje.2002.122966.

345. Marin-Neto JA, Marzullo P, Sousa AC, Marcassa C, Maciel BC, Iazigi N, et al. Radionuclide Angiographic Evidence for Early Predominant Right Ventricular Involvement in Patients with Chagas' Disease. Can J Cardiol. 1988;4(5):231-6.

346. Romano MMD, Moreira HT, Schmidt A, Maciel BC, Marin-Neto JA. Imaging Diagnosis of Right Ventricle Involvement in Cardiomyopathy. Biomed Res Int. 2017;2017:3820191. doi: 10.1155/2017/3820191.

347. Moreira HT, Volpe GJ, Marin-Neto JA, Ambale-Venkatesh B, Nwabuo CC, Trad HS, et al. Evaluation of Right Ventricular Systolic Function in Chagas Disease Using Cardiac Magnetic Resonance Imaging. Circ Cardiovasc Imaging. 2017;10(3):e005571. doi: 10.1161/CIRCIMAGING.116.005571.

348. Moreira HT, Volpe GJ, Marin-Neto JA, Nwabuo CC, Ambale-Venkatesh B, Gali LG, et al. Right Ventricular Systolic Dysfunction in Chagas Disease Defined by Speckle-Tracking Echocardiography: A Comparative Study with Cardiac Magnetic Resonance Imaging. J Am Soc Echocardiogr. 2017;30(5):493-502. doi: 10.1016/j.echo.2017.01.010.

349. Marin-Neto JA, Andrade ZA. Why is there Predominance of Right Heart Failure in Chagas' Disease?. Arq Bras Cardiol. 1991;57(3):181-3.

350. Nunes MC, Rocha MO, Ribeiro ALP, Colosimo EA, Rezende RA, Carmo GA, et al. Right Ventricular Dysfunction is an Independent Predictor of Survival in Patients with Dilated Chronic Chagas' Cardiomyopathy. Int J Cardiol. 2008;127(3):372-9. doi: 10.1016/j.ijcard.2007.06.012.

351. Grupi CJ, Moffa PJ, Barbosa SA, Sanches PC, Barragan Filho EG, Bellotti GM, et al. Holter Monitoring in Chagas' Heart Disease. Sao Paulo Med J. 1995;113(2):835-40. doi: 10.1590/s1516-31801995000200015.

352. Rassi A Jr, Rassi SG, Rassi A. Sudden Death in Chagas' Disease. Arq Bras Cardiol. 2001;76(1):75-96. doi: 10.1590/s0066-782x2001000100008.

353. Sternick EB, Martinelli M, Sampaio R, Gerken LM, Teixeira RA, Scarpelli R, et al. Sudden Cardiac Death in Patients with Chagas Heart Disease and Preserved Left Ventricular Function. J Cardiovasc Electrophysiol. 2006;17(1):113-6. doi: 10.1111/j.1540-8167.2005.00315.x.

354. Martinelli Filho M, Siqueira SF, Moreira H, Fagundes A, Pedrosa A, Nishioka SD, et al. Probability of Occurrence of Life-Threatening Ventricular Arrhythmias in Chagas' Disease versus Non-Chagas' Disease. Pacing Clin Electrophysiol. 2000;23(11 Pt 2):1944-6. doi: 10.1111/j.1540-8159.2000.tb07058.x.

355. Barbosa MP, Rocha MOC, Oliveira AB, Lombardi F, Ribeiro ALP. Efficacy and Safety of Implantable Cardioverter-Defibrillators in Patients with Chagas Disease. Europace. 2013;15(7):957-62. doi: 10.1093/europace/eut011.

356. Cardinalli-Neto A, Greco OT, Bestetti RB. Automatic Implantable Cardioverter-Defibrillators in Chagas' Heart Disease Patients with Malignant Ventricular Arrhythmias. Pacing Clin Electrophysiol. 2006;29(5):467-70. doi: 10.1111/j.1540-8159.2006.00377.x.

357. Sousa AC, Marin-Neto JA, Maciel BC, Gallo L Jr, Amorim DS, Barreto-Martins LE. Systolic and Diastolic Dysfunction in the Indeterminate, Digestive and Chronic Cardiac forms of Chagas' Disease. Arq Bras Cardiol. 1988;50(5):293-9.

358. Nunes MC, Barbosa MM, Ribeiro ALP, Barbosa FB, Rocha MO. Ischemic Cerebrovascular Events in Patients with Chagas Cardiomyopathy: A Prospective Follow-Up Study. J Neurol Sci. 2009;278(1-2):96-101. doi: 10.1016/j.jns.2008.12.015.
359. Oliveira-Filho J, Viana LC, Vieira-de-Melo RM, Faiçal F, Torreão JA, Villar FA, et al. Chagas Disease is an Independent Risk Factor for Stroke: Baseline Characteristics of a Chagas Disease Cohort. Stroke. 2005;36(9):2015-7. doi: 10.1161/01.STR.0000177866.13451.e4.

360. Paixão LC, Ribeiro ALP, Valacio RA, Teixeira AL. Chagas Disease: Independent Risk Factor for Stroke. Stroke. 2009;40(12):3691-4. doi: 10.1161/STROKEAHA.109.560854.

361. Cardoso RN, Macedo FY, Garcia MN, Garcia DC, Benjo AM, Aguilar D, et al. Chagas Cardiomyopathy is Associated with Higher Incidence of Stroke: A Meta-Analysis of Observational Studies. J Card Fail. 2014;20(12):931-8. doi: 10.1016/j.cardfail.2014.09.003.

362. Nunes MC, Kreuser LJ, Ribeiro ALP, Sousa GR, Costa HS, Botoni FA, et al. Prevalence and Risk Factors of Embolic Cerebrovascular Events Associated with Chagas Heart Disease. Glob Heart. 2015;10(3):151-7. doi: 10.1016/j. gheart.2015.07.006.

363. Nunes MC, Barbosa MM, Rocha MO. Peculiar Aspects of Cardiogenic Embolism in Patients with Chagas' Cardiomyopathy: A Transthoracic and Transesophageal Echocardiographic Study. J Am Soc Echocardiogr. 2005;18(7):761-7. doi: 10.1016/j.echo.2005.01.026.

364. Sousa AS, Xavier SS, Freitas GR, Hasslocher-Moreno A. Prevention Strategies of Cardioembolic Ischemic Stroke in Chagas' Disease. Arq Bras Cardiol. 2008;91(5):306-10. doi: 10.1590/s0066-782x2008001700004.

365. Luquetti AO, Rassi A. Diagnóstico Laboratorial da Infecção pelo Trypanosoma cruzi. In: Brener Z, Andrade AZ, Barral-Neto M, editors. Trypanosoma cruzi e Doença de Chagas. Rio de Janeiro: Guanabara Koogan; 2000.

366. Rassi A, Rezende JM, Luquetti AO, Rassi Jr A. Clinical phases and forms of Chagas disease. In: Telleria J, Tibayrenc M, editors. American trypanosomiasis. Chagas disease. One hundred years of research. Amsterdam: Elsevier; 2010.

367. Rodrigues ES, Tavares SBN, Oliveira RA, Siriano LR, Oliveira DEC, Luquetti AO, et al. Existência de Antecedentes Familiares de Doença de Chagas Emindivúdos Atendidos no Laboratório de Pesquisa da Doença de Chagas da UFG entre 2014 e 2017. Cuiabá: Medtrop; 2017.

368. Brasil. Ministério da Saúde. Recomendações sobre o Diagnóstico Parasitológico, Sorológico e Molecular para Confirmação da Doença de Chagas Aguda e Crônica. Rev Patol Trop. 2013;42(4):475-8. doi: 10.5216/ rpt.v42i4.28060.

369. Luquetti AO, Schmuñis GA. Diagnosis of Trypanosoma cruzi Infection. In: Telleria J, Tibayrenc M, editors. American trypanosomiasis. Chagas Disease. One Hundred Years of Research. Amsterdam: Elsevier; 2017.

370. Breniere SF, Carrasco R, Miguez H, Lemesre JL, Carlier Y. Comparisons of immunological Tests for Serodiagnosis of Chagas Disease in Bolivian Patients. Trop Geogr Med. 1985;37(3):231-8.

371. Zeledón R, Dias JC, Brilla-Salazar A, Rezende JM, Vargas LG, Urbina A. Does a Spontaneous Cure for Chagas' Disease Exist? Rev Soc Bras Med Trop. 1988;21(1):15-20. doi: 10.1590/s0037-86821988000100003.

372. Rassi A Jr, Luquetti AO, Tavares SBN, Oliveira RA, Siriano LR, Campos DE, et al. Ausência de Cura Espontânea na Doença de Chagas em 110 Casos sem Tratamento Específico, com Seguimento de 11 a 15 anos. In:: 72th Congresso Brasileiro de Cardiologia; 2017. São Paulo: SBC; 2017.

373. Brasil. Ministério da Saúde. Doença de Chagas Aguda. Aspectos Epidemiológicos, Diagnóstico e Tratamento. Guia de Consulta Rápida para Profissionais de Saúde. Rev Patol Trop. 2007;36(3):1-32.

374. Luquetti AO. El Control de la Transmisión Transfusional. In: Fundación Mundo Sano, editor. La Enfermedad de Chagas a La Puerta de los 100 años Del Conocimiento de una Endemia Americana Ancestral. Buenos Aires: Artes Gráficas Buschi AS; 2007.

375. Andrade AL, Zicker F, Oliveira RM, Silva SA, Luquetti A, Travassos LR, et al. Randomised Trial of Efficacy of Benznidazole in Treatment of Early Trypanosoma cruzi Infection. Lancet. 1996;348(9039):1407-13. doi: 10.1016/s0140-6736(96)04128-1.

376. Estani SS, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C. Efficacy of Chemotherapy with Benznidazole in Children in the Indeterminate Phase of Chagas' Disease. Am J Trop Med Hyg. 1998;59(4):526-9. doi: 10.4269/ ajtmh.1998.59.526. PMID: 9790423..

377. Rassi A, Luquetti AO. Therapy of Chagas´Disease. In: Wendel S, Brener Z, Camargo ME, Rassi A, editors. Chagas´Disease (American trypanosomiasis): Its Impact on Transfusion and Clinical Medicine. São Paulo: Editora ISBT; 1992.

378. Luquetti AO, Rassi A. Tratamiento Específico de la Enfermedad de Chagas en la Fase Crónica: Critérios de Cura Convencionales: Xenodiagnóstico, Hemocultivo y Serología. Rev Patol Trop. 1998;27:37-50. doi: 10.5216/rpt. v27i1.31697.

379. Organización Mundial de la Salud. Organización Panamericana de la Salud. Tratamiento Etiológico de la Enfermedad de Chagas: Conclusiones de Reunión de Especialistas. Rev Patol Trop. 1999;28(2):247-79. doi: 10.5216/rpt. v28i2.31717.

380. Rassi A, Luquetti AO, Rassi GG, Rassi A Jr. Tratamento Específico da Doença de Chagas: Uma Visão de 1962 a 1999. Rev Patol Trop. 2000;29:157-63.

381. Rassi A, Luquetti AO. Specific Treatment for Trypanosoma cruzi Infection (Chagas disease). In: Tyler KM, Miles MA, editors. American Trypanosomiasis. World Class Parasites. Boston: Kluwer Academic Publishers; 2003.

382. Sánchez-Camargo CL, Albajar-Viñas P, Wilkins PP, Nieto J, Leiby DA, Paris L, et al. Comparative Evaluation of 11 Commercialized Rapid Diagnostic Tests for Detecting Trypanosoma cruzi Antibodies in Serum Banks in Areas of Endemicity and Nonendemicity. J Clin Microbiol. 2014;52(7):2506-12. doi: 10.1128/JCM.00144-14.

383. Castro CN, Alves MT, Macedo VO. Importância da Repetição do Xenodiagnóstico para Avaliação da Parasitemia na Fase Crónica da Doença de Chagas. Rev Soc Bras Med Trop. 1983;16(2):98-103. doi: 10.1590/S0037- 86821983000200007.

384. Porrás AI, Yadon ZE, Altcheh J, Britto C, Chaves GC, Flevaud L, et al. Target Product Profile (TPP) for Chagas Disease Point-of-Care Diagnosis and Assessment of Response to Treatment. PLoS Negl Trop Dis. 2015;9(6):e0003697. doi: 10.1371/journal.pntd.0003697.

385. Molina I, Gómez i Prat J, Salvador F, Treviño B, Sulleiro E, Serre N, et al. Randomized Trial of Posaconazole and Benznidazole for Chronic Chagas' Disease. N Engl J Med. 2014;370(20):1899-908. doi: 10.1056/ NEJMoA1313122.

386. Rassi A Jr, Rassi A, Rezende JM. American Trypanosomiasis (Chagas disease). Infect Dis Clin North Am. 2012;26(2):275-91. doi: 10.1016/j. idc.2012.03.002.

387. Bern C. Chagas Disease in the Immunosuppressed Host. Curr Opin Infect Dis. 2012;25(4):450-7. doi: 10.1097/QCO.0b013e328354f179..

388. Cura CI, Lattes R, Nagel C, Gimenez MJ, Blanes M, Calabuig E, et al. Early Molecular Diagnosis of Acute Chagas Disease After Transplantation with Organs from Trypanosoma cruzi-Infected Donors. Am J Transplant. 2013;13(12):3253-61. doi: 10.1111/ajt.12487.

389. Pérez-Molina JA, Rodríguez-Guardado A, Soriano A, Pinazo MJ, Carrilero B, García-Rodríguez M, et al. Guidelines on the Treatment of Chronic Coinfection by Trypanosoma cruzi and HIV Outside Endemic Areas. HIV Clin Trials. 2011;12(6):287-98. doi: 10.1310/hct1206-287.

390. Costa PA, Segatto M, Durso DF, Moreira WJC, Junqueira LL, Castilho FM, et al. Early Polymerase Chain Reaction Detection of Chagas Disease reActivation in Heart Transplant Patients. J Heart Lung Transplant. 2017;36(7):797-805. doi: 10.1016/j.healun.2017.02.018.

391. Diez M, Favaloro L, Bertolotti A, Burgos JM, Vigliano C, Lastra MP, et al. Usefulness of PCR Strategies for Early Diagnosis of Chagas' Disease Reactivation and Treatment Follow-Up in Heart Transplantation. Am J Transplant. 2007;7(6):1633-40. doi: 10.1111/j.1600-6143.2007.01820.x.

392. Burgos JM, Begher SB, Freitas JM, Bisio M, Duffy T, Altcheh J, et al. Molecular Diagnosis and Typing of Trypanosoma cruzi Populations and Lineages in Cerebral Chagas Disease in a Patient with AIDS. Am J Trop Med Hyg. 2005;73(6):1016-8.
393. Ashall F, Yip-Chuck DA, Luquetti AA, Miles MA. Radiolabeled Total Parasite DNA PROBE SPECIFICALLY DETECTS TRYPANOSOMA cruzi in Mammalian Blood. J Clin Microbiol. 1988;26(3):576-8. doi: 10.1128/jcm.26.3.576-578.1988.

394. Moser DR, Kirchhoff LV, Donelson JE. Detection of Trypanosoma cruzi by DNA Amplification Using the Polymerase Chain Reaction. J Clin Microbiol. 1989;27(7):1477-82. doi: 10.1128/jcm.27.7.1477-1482.1989.

395. Avila HA, Pereira JB, Thiemann O, Paiva E, DeGrave W, Morel CM, et al. Detection of Trypanosoma cruzi in Blood Specimens of Chronic Chagasic Patients by Polymerase Chain Reaction Amplification of Kinetoplast Minicircle DNA: Comparison with Serology and Xenodiagnosis. J Clin Microbiol. 1993;31(9):2421-6. doi: 10.1128/jcm.31.9.2421-2426.1993.

396. Britto C, Cardoso MA, Vanni CM, Hasslocher-Moreno A, Xavier SS, Oelemann W, et al. Polymerase Chain Reaction Detection of Trypanosoma cruzi in Human Blood Samples as a Tool for Diagnosis and Treatment Evaluation. Parasitology. 1995;110 (Pt 3):241-7. doi: 10.1017/s0031182000080823.

397. Schijman AG, Altcheh J, Burgos JM, Biancardi M, Bisio M, Levin MJ, et al. Aetiological Treatment of Congenital Chagas' Disease Diagnosed and Monitored by the Polymerase Chain Reaction. J Antimicrob Chemother. 2003;52(3):441-9. doi: 10.1093/jac/dkg338.

398. Britto CC. Usefulness of PCR-Based Assays to Assess Drug Efficacy in Chagas Disease Chemotherapy: Value and limitations. Mem Inst Oswaldo Cruz. 2009;104 Suppl 1:122-35. doi: 10.1590/s0074-02762009000900018.

399. Ramírez JD, Guhl F, Umezawa ES, Morillo CA, Rosas F, Marin-Neto JA, et al. Evaluation of Adult Chronic Chagas' Heart Disease Diagnosis by Molecular and Serological Methods. J Clin Microbiol. 2009;47(12):3945-51. doi: 10.1128/JCM.01601-09.

400. Brasil PE, Castro L, Hasslocher-Moreno AM, Sangenis LH, Braga JU. ELISA versus PCR for Diagnosis of Chronic Chagas Disease: Systematic Review and Meta-Analysis. BMC Infect Dis. 2010;10:337. doi: 10.1186/1471-2334-10-337.

401. Schijman AG. Molecular diagnosis of *Trypanosoma cruzi*. Acta Trop. 2018;184:59-66. doi: 10.1016/j.actatropica.2018.02.019.

402. Schijman AG, Bisio M, Orellana L, Sued M, Duffy T, Jaramillo AMM, et al. International Study to Evaluate PCR Methods for Detection of Trypanosoma cruzi DNA in Blood Samples from Chagas Disease Patients. PLoS Negl Trop Dis. 2011;5(1):e931. doi: 10.1371/journal.pntd.0000931.

403. Ramírez JC, Cura CI, Moreira OC, Lages-Silva E, Juiz N, Velázquez E, et al. Analytical Validation of Quantitative Real-Time PCR Methods for Quantification of Trypanosoma cruzi DNA in Blood Samples from Chagas Disease Patients. J Mol Diagn. 2015;17(5):605-15. doi: 10.1016/j.jmoldx.2015.04.010.

404. Maguire JH, Hoff R, Sherlock I, Guimarães AC, Sleigh AC, Ramos NB, et al. Cardiac Morbidity and Mortality due to Chagas' Disease: Prospective Electrocardiographic Study of a Brazilian Community. Circulation. 1987;75(6):1140-5. doi: 10.1161/01.cir.75.6.1140.

405. Alencar MC, Rocha MO, Lima MM, Costa HS, Sousa GR, Carneiro RC, et al. Heart Rate Recovery in Asymptomatic Patients with Chagas Disease. PLoS One. 2014;9(6):e100753. doi: 10.1371/journal.pone.0100753.

406. Brito BOF, Attia ZI, Martins LNA, Perel P, Nunes MCP, Sabino EC, et al. Left Ventricular Systolic Dysfunction Predicted by Artificial Intelligence Using the Electrocardiogram in Chagas Disease Patients-The SaMi-Trop Cohort. PLoS Negl Trop Dis. 2021;15(12):e0009974. doi: 10.1371/journal.pntd.0009974.

407. Braggion-Santos MF, Moreira HT, Volpe GJ, Koenigkam-Santos M, Marin-Neto JA, Schmidt A. Electrocardiogram Abnormalities in Chronic Chagas Cardiomyopathy correlate with Scar Mass and Left Ventricular Dysfunction as Assessed by cardiac Magnetic Resonance Imaging. J Electrocardiol. 2022;72:66-71. doi: 10.1016/j.jelectrocard.2022.03.005.

408. Rassi A Jr, Rassi A, Little WC, Xavier SS, Rassi SG, Rassi AG, et al. Development and Validation of a Risk Score for Predicting Death in Chagas' Heart Disease. N Engl J Med. 2006;355(8):799-808. doi: 10.1056/NEJMoa053241.

409. Gomes VA, Alves GF, Hadlich M, Azevedo CF, Pereira IM, Santos CR, et al. Analysis of Regional Left Ventricular Strain in Patients with Chagas Disease and Normal Left Ventricular Systolic Function. J Am Soc Echocardiogr. 2016;29(7):679-88. doi: 10.1016/j.echo.2016.03.007.

410. Romano MMD, Moreira HT, Marin-Neto JA, Baccelli PE, Alenezi F, Klem I, et al. Early Impairment of Myocardial Deformation Assessed by Regional Speckle-Tracking Echocardiography in the Indeterminate form of Chagas Disease Without Fibrosis Detected by Cardiac Magnetic Resonance. PLoS Negl Trop Dis. 2020;14(11):e0008795. doi: 10.1371/journal.pntd.0008795.

411. Saraiva RM, Mediano MFF, Quintana MSB, Silva GMS, Costa AR, Sousa AS, et al. Two-Dimensional Strain Derived Parameters Provide Independent Predictors of Progression to Chagas Cardiomyopathy and Mortality in Patients with Chagas disease. Int J Cardiol Heart Vasc. 2022;38:100955. doi: 10.1016/j.ijcha.2022.100955.

412. Santos OR Jr, Rocha MOC, Almeida FR, Cunha PFS, Souza SCS, Saad GP, et al. Speckle Tracking Echocardiographic Deformation Indices in Chagas and Idiopathic Dilated Cardiomyopathy: Incremental Prognostic Value of Longitudinal Strain. PLoS One. 2019;14(8):e0221028. doi: 10.1371/journal.pone.0221028.

413. Barros ML, Ribeiro ALP, Nunes MC, Rocha MO. Association between Left Ventricular Wall Motion Abnormalities And Ventricular Arrhythmia in the Indeterminate form of Chagas Disease. Rev Soc Bras Med Trop. 2011;44(2):213-6. doi: 10.1590/s0037-86822011005000020.

414. Barros MV, Machado FS, Ribeiro ALP, Rocha MO. Diastolic function in Chagas' Disease: An Echo and Tissue Doppler Imaging study. Eur J Echocardiogr. 2004;5(3):182-8. doi: 10.1016/S1525-2167(03)00078-7.

415. Nunes MC, Barbosa MM, Ribeiro ALP, Colosimo EA, Rocha MO. Left atrial Volume Provides Independent Prognostic Value in Patients with Chagas Cardiomyopathy. J Am Soc Echocardiogr. 2009;22(1):82-8. doi: 10.1016/j.echo.2008.11.015.

416. Nunes MP, Colosimo EA, Reis RC, Barbosa MM, Silva JL, Barbosa F, et al. Different Prognostic Impact of the Tissue Doppler-Derived E/e' Ratio on Mortality in Chagas Cardiomyopathy Patients with Heart Failure. J Heart Lung Transplant. 2012;31(6):634-41. doi: 10.1016/j.healun.2012.01.865.

417. Oliveira BM, Botoni FA, Ribeiro ALP, Pinto AS, Reis AM, Nunes MC, et al. Correlation between BNP Levels and Doppler Echocardiographic Parameters of Left Ventricle Filling Pressure in Patients with Chagasic Cardiomyopathy. Echocardiography. 2009;26(5):521-7. doi: 10.1111/j.1540-8175.2008.00842.x.

418. Nascimento CA, Gomes VA, Silva SK, Santos CR, Chambela MC, Madeira FS, et al. Left Atrial and Left Ventricular Diastolic Function in Chronic Chagas disease. J Am Soc Echocardiogr. 2013;26(12):1424-33. doi: 10.1016/j.echo.2013.08.018.

419. Rassi DC, Vieira ML, Arruda AL, Hotta VT, Furtado RG, Rassi DT, et al. Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction. Arq Bras Cardiol. 2014;102(3):245-52. doi: 10.5935/abc.20140003.

420. Mancuso FJ, Almeida DR, Moisés VA, Oliveira WA, Mello ES, Poyares D, et al. Left Atrial Dysfunction in Chagas Cardiomyopathy is More Severe than in Idiopathic Dilated Cardiomyopathy: A Study with Real-time Three-dimensional Echocardiography. J Am Soc Echocardiogr. 2011;24:526-532. doi: 10.1016/j.echo.2011.01.013.

421. Saraiva RM, Pacheco NP, Pereira TOJS, Costa AR, Holanda MT, Sangenis LHC, ET AL. Left Atrial Structure and Function Predictors of New-Onset Atrial Fibrillation in Patients with Chagas Disease. J Am Soc Echocardiogr. 2020;33(11):1363-74.e1. doi: 10.1016/j.echo.2020.06.003.

422. Acquatella H, Pérez JE, Condado JA, Sánchez I. Limited Myocardial Contractile Reserve and Chronotropic Incompetence in Patients with Chronic Chagas' Disease: Assessment by Dobutamine Stress Echocardiography. J Am Coll Cardiol. 1999;33(2):522-9. doi: 10.1016/s0735-1097(98)00569-5.
423. Rassi DC, Hotta VT, Furtado RG, Vieira MLC, Turco FP, Melato LH, Nunes CG, Rassi L Jr, Rassi S. Incidence and Variables Associated with Arrhythmias During Dobutamine-Atropine Stress Echocardiography Among Patients with Chagas Disease. Echocardiography. 2019;36(7):1338-45. doi: 10.1111/echo.14341.

424. Senra T, Ianni BM, Costa ACP, Mady C, Martinelli-Filho M, Kalil-Filho R, et al. Long-Term Prognostic Value of Myocardial Fibrosis in Patients with Chagas Cardiomyopathy. J Am Coll Cardiol. 2018;72(21):2577-87. doi: 10.1016/j.jacc.2018.08.2195.

425. Pinheiro MVT, Moll-Bernardes RJ, Camargo GC, Siqueira FP, Azevedo CF, Holanda MT, et al. Associations between Cardiac Magnetic Resonance T1 Mapping Parameters and Ventricular Arrhythmia in Patients with Chagas Disease. Am J Trop Med Hyg. 2020;103(2):745-51. doi: 10.4269/ajtmh.20-0122.

426. Falchetto EB, Costa SC, Rochitte CE. Diagnostic Challenges of Chagas Cardiomyopathy and CMR Imaging. Glob Heart. 2015;10(3):181-7. doi: 10.1016/j.gheart.2015.07.005.

427. Weinsaft JW, Kim HW, Shah DJ, Klem I, Crowley AL, Brosnan R, et al. Detection of Left Ventricular Thrombus by Delayed-Enhancement Cardiovascular Magnetic Resonance Prevalence and Markers in Patients with Systolic Dysfunction. J Am Coll Cardiol. 2008;52(2):148-57. doi: 10.1016/j.jacc.2008.03.041. PMID: 18598895.

428. Volpe GJ, Moreira HT, Trad HS, Wu KC, Braggion-Santos MF, Santos MK, et al. Left Ventricular Scar and Prognosis in Chronic Chagas Cardiomyopathy. J Am Coll Cardiol. 2018;72(21):2567-76. doi: 10.1016/j.jacc.2018.09.035.

429. Senra T, Rochitte CE. Reply: Rassi Score: Another External Validation with High Performance in Patients with Chagas Cardiomyopathy. J Am Coll Cardiol. 2019;73(13):1735-37. doi: 10.1016/j.jacc.2019.02.007.

430. Torres RM, Correia D, Nunes MDCP, Dutra WO, Talvani A, Sousa AS, et al. Prognosis of Chronic Chagas Heart Disease and Other Pending Clinical Challenges. Mem Inst Oswaldo Cruz. 2022;117:e210172. doi: 10.1590/0074-02760210172.

431. Mastrocola LE, Amorim BJ, Vitola JV, Brandão SCS, Grossman GB, Lima RSL, et al. Update of the Brazilian Guideline on Nuclear Cardiology - 2020. Arq Bras Cardiol. 2020;114(2):325-429. doi: 10.36660/abc.20200087.

432. Sara L, Szarf G, Tachibana A, Shiozaki AA, Villa AV, Oliveira AC, et al. II Guidelines on Cardiovascular Magnetic Resonance and Computed Tomography of the Brazilian Society of Cardiology and the Brazilian College of Radiology. Arq Bras Cardiol. 2014;103(6 Suppl 3):1-86. doi: 10.5935/abc.20145006.

433. Pimenta J, Miranda M, Silva LA. Abnormal Atrioventricular Nodal Response Patterns in Patients with Long-Term Chagas' Disease. Chest. 1980;78(2):310-5. doi: 10.1378/chest.78.2.310.

434. Towbin JA, McKenna WJ, Abrams DJ, Ackerman MJ, Calkins H, Darrieux FCC, et al. 2019 HRS Expert Consensus Statement on Evaluation, Risk Stratification, and Management of Arrhythmogenic Cardiomyopathy. Heart Rhythm. 2019;16(11):e301-e372. doi: 10.1016/j.hrthm.2019.05.007.

435. Silva NCF, Reis MDCM, Póvoa RMDS, Paola AAV, Luna Filho B. Ventricular arrhythmias in the Chagas disease are Not Random Phenomena: Long-term Monitoring in Chagas Arrhythmias. J Cardiovasc Electrophysiol. 2019;30(11):2370-2376. doi: 10.1111/jce.14162.

436. Ribeiro ALP, Cavalvanti PS, Lombardi F, Nunes MC, Barros MV, Rocha MO. Prognostic Value of Signal-Averaged Electrocardiogram in Chagas Disease. J Cardiovasc Electrophysiol. 2008;19(5):502-9. doi: 10.1111/j.1540-8167.2007.01088.x.

437. Resende LA, Molina RJ, Ferreira BD, Carneiro AC, Ferreira LA, Silva VJ, et al. Cardiac Autonomic Function in Chagasic Elderly Patients in an Endemic Area: A time and Frequency Domain Analysis Approach. Auton Neurosci. 2007;131(1-2):94-101. doi: 10.1016/j.autneu.2006.05.005.

438. Vasconcelos DF, Junqueira LF Jr. Distinctive Impaired Cardiac Autonomic Modulation of Heart Rate Variability in Chronic Chagas' Indeterminate and Heart Diseases. J Electrocardiol. 2009;42(3):281-9. doi: 10.1016/j.j electrocard.2008.10.007.

439. Alberto AC, Pedrosa RC, Zarzoso V, Nadal J. Association between Circadian Holter ECG Changes and Sudden Cardiac Death in Patients with Chagas Heart Disease. Physiol Meas. 2020;41(2):025006. doi: 10.1088/1361-6579/ab6ebc.

440. Silva LEV, Moreira HT, Bernardo MMM, Schmidt A, Romano MMD, Salgado HC et al. Prediction of Echocardiographic Parameters in Chagas Disease Using Heart Rate Variability and Machine Learning. Biomed Signal Process Control. 2021;67:102513. Doi: 10.1016/j.bspc.2021.102513.

441. Silva LEV, Moreira HT, Oliveira MM, Cintra LSS, Salgado HC, Fazan RJr, et al. Heart Rate Variability as a Biomarker in Patients with Chronic Chagas Cardiomyopathy with or Without Concomitant Digestive Involvement and its Relationship with the Rassi Score. Biomed Eng Online. 2022;21(1):44. doi: 10.1186/s12938-022-01014-6.

442. Martinelli Filho M, Sosa E, Nishioka S, Scanavacca M, Bellotti G, Pileggi F. Clinical and Electrophysiologic Features of Syncope in Chronic Chagasic Heart Disease. J Cardiovasc Electrophysiol. 1994;5(7):563-70. doi: 10.1111/j.1540-8167.1994.tb01297.x.

443. Costa HS, Lima MMO, Figueiredo PHS, Lima VP, Ávila MR, Menezes KKP, et al. Exercise Tests in Chagas Cardiomyopathy: An Overview of Functional Evaluation, Prognostic Significance, and Current Challenges. Rev Soc Bras Med Trop. 2020;53:e20200100. doi: 10.1590/0037-8682-0100-2020.

444. Lima MM, Nunes MC, Rocha MO, Beloti FR, Alencar MC, Ribeiro ALP. Left Ventricular Diastolic Function and Exercise Capacity in Patients with Chagas Cardiomyopathy. Echocardiography. 2010;27(5):519-24. doi: 10.1111/j.1540-8175.2009.01081.x.

445. Carvalho G, Rassi S, Bastos JM, Câmara SS. Asymptomatic Coronary Artery Disease in Chagasic Patients with Heart Failure: Prevalence and risk Factors. Arq Bras Cardiol. 2011;97(5):408-12. doi: 10.1590/s0066-782x2011005000103.

446. Campos FA, Magalhães ML, Moreira HT, Pavão RB, Lima Filho MO, Lago IM, et al. Chagas Cardiomyopathy as the Etiology of Suspected Coronary Microvascular Disease. A Comparison Study with Suspected Coronary Microvascular Disease of Other Etiologies. Arq Bras Cardiol. 2020;115(6):1094-1101. doi: 10.36660/abc.20200381.

447. Pavão RB, Moreira HT, Pintya AO, Haddad JL, Badran AV, Lima Filho MO, et al. Aspirin Plus Verapamil Relieves Angina and Perfusion Abnormalities in Patients with Coronary Microvascular Dysfunction and Chagas Disease: A Pilot Non-Randomized Study. Rev Soc Bras Med Trop. 2021;54:e0181. doi: 10.1590/0037-8682-0181-2021.

448. Chadalawada S, Rassi A Jr, Samara O, Monzon A, Gudapati D, Barahona LV, et al. Mortality Risk in Chronic Chagas Cardiomyopathy: A Systematic Review and Meta-Analysis. ESC Heart Fail. 2021;8(6):5466-5481. doi: 10.1002/ehf2.13648.

449. Cowley LE, Farewell DM, Maguire S, Kemp AM. Methodological Standards for the Development and Evaluation of Clinical Prediction Rules: A Review of the Literature. Diagn Progn Res. 2019;3:16. doi: 10.1186/s41512-019-0060-y.

450. Rocha MO, Ribeiro ALP. A Risk Score for Predicting Death in Chagas' Heart Disease. N Engl J Med. 2006;355(23):2488-9. doi: 10.1056/NEJMc062580.

451. Benchimol-Barbosa PR, Tura BR, Barbosa EC, Kantharia BK. Utility of a Novel Risk Score for Prediction of Ventricular Tachycardia and Cardiac Death in Chronic Chagas Disease - the SEARCH-RIO Study. Braz J Med Biol Res. 2013;46(11):974-84. doi: 10.1590/1414-431X20133141.

452. Peña CMM, Reis MS, Pereira BB, Nascimento EMD, Pedrosa RC. Dysautonomy in Different Death Risk Groups (Rassi Score) in Patients with Chagas Heart Disease. Pacing Clin Electrophysiol. 2018;41(3):238-45. doi: 10.1111/pace.13270.

453. Uellendahl M, Siqueira ME, Calado EB, Kalil-Filho R, Sobral D, Ribeiro C, et al. Cardiac Magnetic Resonance-Verified Myocardial Fibrosis in Chagas Disease: Clinical Correlates and Risk Stratification. Arq Bras Cardiol. 2016;107(5):460-6. doi: 10.5935/abc.20160168.
454. Valdigem BP, Andalaft RB, Moreira DAR, Faria LR, Oliveira FG, Pimenta DA, et al. Clinical Scores Can Infer Risk of VT Induction in Chagas Disease Patients. Eur Heart J. 2018;39: suppl_1 ehy565.P2914. doi: 10.1093/eurheartj/ehy565.P2914.

455. Silva RRD, Reis MS, Pereira BB, Nascimento EMD, Pedrosa RC. Additional Value of Anaerobic Threshold in a General Mortality Prediction Model in a Urban Patient Cohort with Chagas Cardiomyopathy. Rev Port Cardiol. 2017;36(12):927-34. doi: 10.1016/j.repc.2017.06.012.

456. Duarte JO, Magalhães LP, Santana OO, Silva LB, Simões M, Azevedo DO, et al. Prevalence and Prognostic Value of Ventricular Dyssynchrony in Chagas Cardiomyopathy. Arq Bras Cardiol. 2011;96(4):300-6. doi: 10.1590/s0066-782x2011005000037.

457. Ritt LE, Carvalho AC, Feitosa GS, Pinho-Filho JA, Andrade MV, Feitosa-Filho GS, et al. Cardiopulmonary Exercise and 6-min Walk Tests as Predictors of Quality of Life and Long-Term Mortality Among Patients with Heart Failure due to Chagas Disease. Int J Cardiol. 2013;168(4):4584-5. doi: 10.1016/j.ijcard.2013.06.064.

458. Rassi A Jr, Rassi A, Rassi SG. Predictors of Mortality in Chronic Chagas Disease: A Systematic Review of Observational Studies. Circulation. 2007;115(9):1101-8. doi: 10.1161/CIRCULATIONAHA.106.627265.

459. Nielsen JC, Lin YJ, Figueiredo MJO, Shamloo AS, Alfie A, Boveda S, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus on Risk Assessment in Cardiac Arrhythmias: Use the Right Tool for the Right Outcome, in the Right Population. Europace. 2020;22(8):1147-8. doi: 10.1093/europace/euaa065.

460. Martinelli M, Rassi A Jr, Marin-Neto JA, Paola AA, Berwanger O, Scanavacca MI, et al. CHronic use of Amiodarone aGAINSt Implantable cardioverter-defibrillator Therapy for Primary Prevention of Death in Patients with Chagas Cardiomyopathy Study: Rationale and Design of a Randomized Clinical Trial. Am Heart J. 2013;166(6):976-982.e4. doi: 10.1016/j.ahj.2013.08.027.

461. Mady C, Cardoso RH, Barretto AC, Luz PL, Bellotti G, Pileggi F. Survival and Predictors of Survival in Patients with Congestive Heart Failure due to Chagas' Cardiomyopathy. Circulation. 1994;90(6):3098-102. doi: 10.1161/01.cir.90.6.3098.

462. Barbosa PRB. Noninvasive Prognostic Markers for Cardiac Death and Ventricular Arrhythmia in Long-Term Follow-Up of Subjects with Chronic Chagas' Disease. Braz J Med Biol Res. 2007;40(2):167-78. doi: 10.1590/S0100-879X2006005000061.

463. Souza AC, Salles G, Hasslocher-Moreno AM, Sousa AS, Brasil PEAAB, Saraiva RM, et al. Development of a Risk Score to Predict Sudden Death in Patients with Chaga's Heart Disease. Int J Cardiol. 2015;187:700-4. doi: 10.1016/j.ijcard.2015.03.372.

464. Romano MMD, Moreira HT, Alenezi F, Saraiva LAL, Schmidt A, Maciel BC, et al. Prognostic Value of Speckle Tracking Echocardiography in Patients with Chagas Cardiomyopathy. Eur Heart J Cardiovasc Imaging. 2017;18(3):146. doi: 10.1093/ehjci/jex286.

465. Junqueira LF Jr. Insights Into the Clinical and Functional Significance of Cardiac Autonomic Dysfunction in Chagas Disease. Rev Soc Bras Med Trop. 2012;45(2):243-52. doi: 10.1590/s0037-86822012000200020.

466. Ribeiro ALP, Rocha MO, Terranova P, Cesarano M, Nunes MD, Lombardi F. T-Wave Amplitude Variability and the Risk of Death in Chagas Disease. J Cardiovasc Electrophysiol. 2011;22(7):799-805. doi: 10.1111/j.1540-8167.2010.02000.x.

467. Salles GF, Xavier SS, Sousa AS, Hasslocher-Moreno A, Cardoso CR. T-Wave Axis Deviation as an Independent Predictor of Mortality in Chronic Chagas' Disease. Am J Cardiol. 2004;93(9):1136-40. doi: 10.1016/j.amjcard.2004.01.040.

468. Salles G, Xavier S, Sousa A, Hasslocher-Moreno A, Cardoso C. Prognostic Value of QT Interval Parameters for Mortality Risk Stratification in Chagas' Disease: Results of a Long-Term Follow-Up Study. Circulation. 2003;108(3):305-12. doi: 10.1161/01.CIR.0000079174.13444.9C.

469. Oliveira CDL, Nunes MCP, Colosimo EA, Lima EM, Cardoso CS, Ferreira AM, et al. Risk Score for Predicting 2-Year Mortality in Patients with Chagas Cardiomyopathy from Endemic Areas: SaMi-Trop Cohort Study. J Am Heart Assoc. 2020;9(6):e014176. doi: 10.1161/JAHA.119.014176.

470. Rubim VS, Drumond Neto C, Romeo JL, Montera MW. Prognostic Value of the Six-Minute Walk Test in Heart Failure. Arq Bras Cardiol. 2006;86(2):120-5. doi: 10.1590/s0066-782x2006000200007.

471. Lima-Costa MF, Cesar CC, Peixoto SV, Ribeiro ALP. Plasma B-Type Natriuretic Peptide as a Predictor of Mortality in Community-Dwelling Older Adults with Chagas Disease: 10-Year Follow-Up of the Bambui Cohort Study of Aging. Am J Epidemiol. 2010;172(2):190-6. doi: 10.1093/aje/kwq106.

472. Sherbuk JE, Okamoto EE, Marks MA, Fortuny E, Clark EH, Galdos-Cardenas G, et al. Biomarkers and Mortality in Severe Chagas Cardiomyopathy. Glob Heart. 2015;10(3):173-80. doi: 10.1016/j.gheart.2015.07.003.

473. Mendes FSNS, Brasil PEAAD. Prediction Models for Decision-Making on Chagas Disease. Arq Bras Cardiol. 2017;108(5):470-2. doi: 10.5935/abc.20170059.

474. Marin-Neto JA, Rassi A Jr. The Challenge of Risk Assessment in the Riddle of Chagas Heart Disease. Mem Inst Oswaldo Cruz. 2022;117:e210172chgsb. doi: 10.1590/0074-02760210172chgsb.

475. Oliveira CDL, Cardoso CS, Baldoni NR, Natany L, Ferreira AM, Oliveira LC, et al. Cohort Profile Update: the Main and New Findings from the SaMi-Trop Chagas Cohort. Rev Inst Med Trop Sao Paulo. 2021;63:e75. doi: 10.1590/S1678-9946202163075.

476. Senra T. Avaliação da Fibrose Miocárdica pela Ressonância Magnética Cardíaca na Estratificação Prognóstica na Miocardiopatia Chágásica [dissertation]. São Paulo: Universidade de São Paulo; 2018. doi: 10.11606/T.5.2018.tde-12092018-093643.

477. Rassi A Jr, Rassi A. Rassi Score: Another External Validation with High Performance in Patients with Chagas Cardiomyopathy. J Am Coll Cardiol. 2019;73(13):1734-5. doi: 10.1016/j.jacc.2018.12.079.

478. Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS. Evaluating the Added Predictive Ability of a New Marker: from Area Under the ROC Curve to Reclassification and Beyond. Stat Med. 2008;27(2):157-72. doi: 10.1002/sim.2929.

479. Scanavacca M, Sosa E. Electrophysiologic Study in Chronic Chagas' Heart Disease. Sao Paulo Med J. 1995;113(2):841-50. doi: 10.1590/s1516-31801995000200016.

480. Silva RM, Távora MZ, Gondim FA, Metha N, Hara VM, Paola AA. Predictive Value of Clinical and Electrophysiological Variables in Patients with Chronic Chagasic Cardiomyopathy and Nonsustained Ventricular Tachycardia. Arq Bras Cardiol. 2000;75(1):33-47. doi: 10.1590/s0066-782x2000000700004.

481. Leite LR, Fenelon G, Simoes A Jr, Silva GG, Friedman PA, Paola AA. Clinical Usefulness of Electrophysiologic Testing in Patients with Ventricular Tachycardia and Chronic Chagasic Cardiomyopathy Treated with Amiodarone or Sotalol. J Cardiovasc Electrophysiol. 2003;14(6):567-73. doi: 10.1046/j.1540-8167.2003.02278.x.

482. Chagas C. The discovery of Trypanosoma Cruzi and of American Trypanosomiasis: Historic Retrospect. Mem Inst Oswaldo Cruz. 1922;15(1):1-11.

483. Rassi A, Rassi A Jr. Forma indeterminada da doença de Chagas. In: Porto CC, editor. Doenças do Coração: Prevenção e Tratamento. Rio de Janeiro: Guanabara Koogan; 1998.

484. Hasslocher-Moreno AM, Xavier SS, Saraiva RM, Sousa AS. Indeterminate form of Chagas Disease: Historical, Conceptual, Clinical, and Prognostic Aspects. Rev Soc Bras Med Trop. 2021;54:e02542021. doi: 10.1590/0037-8682-0254-2021.

485. Biolo A, Ribeiro ALP, Clausell N. Chagas Cardiomyopathy--Where do we Stand After a Hundred Years? Prog Cardiovasc Dis. 2010;52(4):300-16. doi: 10.1016/j.pcad.2009.11.008.
# Guidelines

486. Terzi FVO, Siqueira Filho AG, Nascimento EM, Pereira BB, Pedrosa RC. Regional Left Ventricular Dysfunction and its Association with Complex Ventricular Arrhythmia, in Chagasic Patients with Normal or Borderline Electrocardiogram. Rev Soc Bras Med Trop. 2010;43(5):557-61. doi: 10.1590/S0037-86822010000500017.

487. Pinto AS, Oliveira BM, Botoni FA, Ribeiro ALP, Rocha MO. Myocardial Dysfunction in Chagasic Patients with no Apparent Heart Disease. Arq Bras Cardiol. 2007;89(6):385-90. doi: 10.1590/s0066-782x2007001800006.

488. Almeida-Filho OC, Maciel BC, Schmidt A, Pazin-Filho A, Marin-Neto JA. Minor Segmental Dyssynergy Reflects Extensive Myocardial Damage and Global Left Ventricle Dysfunction in Chronic Chagas disease. J Am Soc Echocardiogr. 2002;15(6):610-6. doi: 10.1067/mje.2002.117845.

489. Cianciulli TF, Albarracín GA, Llobera MN, Prado NG, Saccheri MC, Vásquez YMH, et al. Speckle Tracking Echocardiography in the Indeterminate form of Chagas Disease. Echocardiography. 2021;38(1):39-46. doi: 10.1111/echo.14917.

490. Costa HS, Nunes MC, Souza AC, Lima MM, Carneiro RB, Sousa GR, et al. Exercise-Induced Ventricular Arrhythmias and Vagal Dysfunction in Chagas disease Patients with no Apparent Cardiac Involvement. Rev Soc Bras Med Trop. 2015;48(2):175-80. doi: 10.1590/0037-8682-0295-2014.

491. Crudo N, Gagliardi J, Piombo A, Castellano JL, Riccitelli MA. Hallazgos Ergométricos en Pacientes Chagásicos, Asintomáticos, con Electrocardiograma Normal y sin Cardiopatía Evidenciable. Rev Argent Cardiol. 2012;80(6):471-7. doi: 10.7775/rac.es.v80.i6.1356.

492. Almeida JWR, Shikanai-Yasuda MA, Amato Neto V, Castilho EA, Barretto ACP. Estudo da Forma Indeterminada da Doença de Chagas através da Eletrocardiografia Dinâmica. Rev Inst Med Trop Sao Paulo. 1982;24(4):222-8.

493. Marins N, Flores AP, Seixas TN, Fagundes JC, Ostrowsky M, Martins ADM, et al. Dynamic Electrocardiography in Chagas' Patients with the Indeterminate form or Without Apparent Cardiopathy. Arq Bras Cardiol. 1982;39(5):303-7.

494. Barretto ACP, Bellotti G, Sosa E, Grupi C, Mady C, Ianni BM, et al. Arrhythmias and the Indeterminate form of Chagas' Disease. Arq Bras Cardiol. 1986;47(3):197-9.

495. Marques DS, Canesin MF, Barutta F Jr, Fuganti CJ, Barretto AC. Evaluation of Asymptomatic Patients with Chronic Chagas Disease Through Ambulatory Electrocardiogram, Echocardiogram and B-Type Natriuretic Peptide Analyses. Arq Bras Cardiol. 2006;87(3):336-43. doi: 10.1590/s0066-782x2006001600017.

496. Acha RE, Rezende MT, Heredia RAG, Silva AC, Rezende ES, Souza CA. Prevalence of Cardiac Arrhythmias During and After Pregnancy in Women with Chagas' Disease Without Apparent Heart Disease. Arq Bras Cardiol. 2002;79(1):1-9.

497. Junqueira Júnior LF, Gallo Júnior L, Manço JC, Marin-Neto JA, Amorim DS. Subtle Cardiac Autonomic Impairment in Chagas' Disease Detected by Baroreflex Sensitivity Testing. Braz J Med Biol Res. 1985;18(2):171-8. doi: 10.1590/S0066-782X200200100001.

498. Amorim DD, Marin-Neto JA. Functional Alterations of the Autonomic Nervous System in Chagas' Heart Disease. Sao Paulo Med J. 1995;113(2):772-84. doi: 10.1590/s1516-31801995000200007.

499. Molina RB, Matsubara BB, Hueb JC, Zanati SG, Meira DA, Cassolato JL, et al. Dysautonomia and Ventricular Dysfunction in the Indeterminate form of Chagas Disease. Int J Cardiol. 2006;113(2):188-93. doi: 10.1016/j.ijcard.2005.11.010.

500. Abuhid IM, Pedroso ER, Rezende NA. Scintigraphy for the Detection of Myocardial Damage in the Indeterminate Form of Chagas Disease. Arq Bras Cardiol. 2010;95(1):30-4. doi: 10.1590/s0066-782x201000500006.

501. Peix A, García R, Sánchez J, Cabrera LO, Padrón K, Vedia O, et al. Myocardial Perfusion Imaging and Cardiac Involvement in the Indeterminate Phase of Chagas Disease. Arq Bras Cardiol. 2013;100(2):114-7. doi: 10.5935/abc.20130023.

502. Mady C, Moraes AV, Galiano N, Décourt LV. Hemodynamic Study of the Indeterminate form of Chagas' Disease. Arq Bras Cardiol. 1982;38(4):271-5.

503. Noya-Rabelo MM, Macedo CT, Larocca T, Machado A, Pacheco T, Torreão J, et al. The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas' Disease: A Study Using Magnetic Resonance. Arq Bras Cardiol. 2018;110(2):124-31. doi: 10.5935/abc.20180016.

504. Regueiro A, García-Álvarez A, Sitges M, Ortiz-Pérez JT, De Caralt MT, Pinazo MJ, et al. Myocardial Involvement in Chagas Disease: Insights from Cardiac Magnetic Resonance. Int J Cardiol. 2013;165(1):107-12. doi: 10.1016/j.ijcard.2011.07.089.

505. Mady C, Barretto AC, Stolf N, Lopes EA, Dauar D, Wajngarten M, et al. Endomyocardial Biopsy in the Indeterminate Form of Chagas' Disease. Arq Bras Cardiol. 1981;36(6):387-90.

506. Barretto AC, Amato Neto V. Subsidies for the new concept of the indeterminate form of Chagas' disease. Rev Hosp Clin Fac Med Sao Paulo. 1986;41(6):249-53.

507. Amor M, Rousse MG, Schmitt G, Velázquez R, Flores JF, Acunzo RS, et al. Utilidad del Strain Bidimensional Longitudinal por Speckle Tracking en Pacientes con Enfermedad de Chagas-Mazza sin Cardiopatía Demostrada. Insuf Card. 2016;11(1):2-9.

508. Furtado RG, Frota DC, Silva JB, Romano MM, Almeida Filho OC, Schmidt A, et al. Right Ventricular Doppler Echocardiographic Study of Indeterminate Form of Chagas Disease. Arq Bras Cardiol. 2015;104(3):209-17. doi: 10.5935/abc.20140197.

509. Hasslocher-Moreno AM, Xavier SS, Saraiva RM, Sangenis LHC, Holanda MT, Veloso HH, et al. 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. Trop Med Infect Dis. 2020;5(2):76. doi: 10.3390/tropicalmed5020076.

510. Macêdo V. Influência da Exposição à Reinfecção na Evolução da Doença de Chagas. Rev Pat Trop. 1976;5:33-116.

511. Basquiera AL, Sembaj A, Aguerri AM, Omelianiuk M, Guzmán S, Barral JM, et al. Risk Progression to Chronic Chagas Cardiomyopathy: Influence of Male Sex and of Parasitaemia Detected by Polymerase Chain Reaction. Heart. 2003;89(10):1186-90. doi: 10.1136/heart.89.10.1186.

512. Ferreira AM, Sabino ÉC, Oliveira LC, Oliveira CDL, Cardoso CS, Ribeiro ALP, et al. Impact of the Social Context on the Prognosis of Chagas Disease Patients: Multilevel Analysis of a Brazilian Cohort. PLoS Negl Trop Dis. 2020;14(6):e0008399. doi: 10.1371/journal.pntd.0008399.

513. Eberhardt N, Sanmarco LM, Bergero G, Favaloro RR, Vigliano C, Aoki MP. HIF-1α and CD73 Expression in Cardiac Leukocytes Correlates with the Severity of Myocarditis in End-stage Chagas Disease Patients. Leukoc Biol. 2021;109(1):233-44. doi: 10.1002/JLB.4MA0420-125R.

514. Ayo CM, Dalalio MM, Visentainer JE, Reis PG, Sippert EÂ, Jarduli LR, et al. Genetic Susceptibility to Chagas Disease: An Overview About the Infection and About the Association Between Disease and the Immune Response Genes. Biomed Res Int. 2013;2013:284729. doi: 10.1155/2013/284729.

515. Sousa GR, Costa HS, Souza AC, Nunes MC, Lima MM, Rocha MO. Health-related quality of Life in Patients with Chagas Disease: A Review of the Evidence. Rev Soc Bras Med Trop. 2015;48(2):121-8. doi: 10.1590/0037-8682-0244-2014.

516. Castilhos MP, Huguenin GVB, Rodrigues PRM, Nascimento EMD, Pereira BB, Pedrosa RC. Diet Quality of Patients with Chronic Chagas Disease in a Tertiary Hospital: A Case-control Study. Rev Soc Bras Med Trop. 2017;50(6):795-804. doi: 10.1590/0037-8682-0237-2017.

517. Echeverría LE, Rojas LZ, López LA, Rueda-Ochoa OL, Gómez-Ochoa SA, Morillo CA. Myocardial Involvement in Chagas Disease and Insulin Resistance: A Non-metabolic Model of Cardiomyopathy. Glob Heart. 2020;15(1):36. doi: 10.5334/gh.793.
518. Pereira JB, Willcox HP, Coura JR. Morbidity of Chagas disease: III. Six-year Longitudinal Study, At Virgem da Lapa, MG, Brazil. Mem Inst Oswaldo Cruz. 1985;80(1):63-71. doi: 10.1590/S0074-02761985000100010.

519. Gonzáles J, Azzato F, Ambrosio G, Milei J. Sudden Death in Indeterminate Chagas Disease is Uncommon. A Systematic Review. Rev Argent Cardiol. 2012;80(3):240-6.

520. Gonzáles J, Fragola JPO, Azzato F, Milei J. Sudden Death is Uncommon in Chronic Chagas Disease without Evident Heart Disease. Rev Argent Cardiol.2019;87:52-4.

521. Machado-de-Assis GF, Diniz GA, Montoya RA, Dias JC, Coura JR, Machado-Coelho GL, et al. A Serological, Parasitological and Clinical Evaluation of Untreated Chagas Disease Patients and Those Treated with Benznidazole Before and Thirteen Years After Intervention. Mem Inst Oswaldo Cruz. 2013;108(7):873-80. doi: 10.1590/0074-0276130122.

522. Dias JC, Kloetzel K. The Prognostic Value of the Electrocardiographic Features of Chronic Chagas' Disease. Rev Inst Med Trop Sao Paulo. 1968;10(3):158-62.

523. Alves RM, Thomaz RP, Almeida EA, Wanderley JS, Guariento ME. Chagas' Disease and Ageing: The Coexistence of Other Chronic Diseases with Chagas' Disease in Elderly Patients. Rev Soc Bras Med Trop. 2009;42(6):622-8. doi: 10.1590/s0037-86822009000600002.

524. Gurgel CB, Almeida EA. Frequency of Hypertension in Patients with Chronic Chagas Disease and its Consequences on the Heart: A Clinical and Pathological Study. Arq Bras Cardiol. 2007;89(3):174-82. doi: 10.1590/s0066-782x2007001500008.

525. Ianni BM, Mady C, Arteaga E, Fernandes F. Cardiovascular Diseases Observed During Follow-up of a Group of Patients with Undetermined Form of Chagas' Disease. Arq Bras Cardiol. 1998;71(1):21-4. doi: 10.1590/s0066-782x1998000700005.

526. Guariento ME, Alegre SM, Souza LRME. Evolução Clínica de Pacientes Chagásicos Acompanhados em um Serviço de Referência. Rev Soc Bras Med Trop. 2002;35(Supl III):206-7.

527. Guariento ME, Orosz JE, Gontijo JA. Clinical Relationship Between Chagas' Disease and Primary Arterial Hypertension at an Outpatient Referral Service. Arq Bras Cardiol. 1998;70(6):431-4. doi: 10.1590/s0066-782x1998000600009.

528. Saraiva RM, Mediano MFF, Mendes FS, Silva GMS, Veloso HH, Sangenis LHC, et al. Chagas Heart Disease: An Overview of Diagnosis, Manifestations, Treatment, and Care. World J Cardiol. 2021;13(12):654-75. doi: 10.4330/wjc.v13.i12.654.

529. Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, Drug Safety, and Effectiveness of Etiological Treatment Programs for Chagas Disease in Honduras, Guatemala, and Bolivia: 10-year Experience of Médecins Sans Frontières. PLoS Negl Trop Dis. 2009;3(7):e488. doi: 10.1371/journal.pntd.0000488.

530. Mahoney RT, Morel CM. A Global Health Innovation System (GHIS). Innovation Strategy Today. 2006;2(1):1-12.

531. Torrico F, Gascón J, Barreira F, Blum B, Almeida IC, Alonso-Vega C, et al. New Regimens of Benznidazole Monotherapy and in Combination with Fosruconazole for Treatment of Chagas Disease (BENDITA): A Phase 2, Double-blind, Randomised Trial. Lancet Infect Dis. 2021;21(8):1129-40. doi: 10.1016/S1473-3099(20)30844-6.

532. García MC, Eberhardt N, Sanmarco LM, Ponce NE, Jimenez-Kairuz AF, Aoki MP. Improved Efficacy and Safety of Low Doses of Benznidazole-loaded Multiparticulate Delivery Systems in Experimental Chagas Disease Therapy. Eur J Pharm Sci. 2021;164:105912. doi: 10.1016/j.ejps.2021.105912.

533. Bulla D, Luquetti A, Sánchez M, Estani SS, Salvatella R. Basic Decalogue for Care of Chagas's Disease at Primary Level. Rev Chilena Infectol. 2014;31(5):588-9. doi: 10.4067/S0716-10182014000500011.

534. Falk N, Berenstein AJ, Moscatelli G, Moroni S, González N, Ballering G, et al. Effectiveness of Nifurtimox in the Treatment of Chagas Disease:

a Long-Term Retrospective Cohort Study in Children and Adults. Antimicrob Agents Chemother. 2022;66(5):e0202121. doi: 10.1128/acm.02021-21.

535. Thakare R, Dasgupta A, Chopra S. Update on Nifurtimox for Treatment of Chagas Disease. Drugs Today (Barc). 2021;57(4):251-63. doi: 10.1358/dot.2021.57.4.3251712.

536. Malone CJ, Nevis I, Fernández E, Sanchez A. A Rapid Review on the Efficacy and Safety of Pharmacological Treatments for Chagas Disease. Trop Med Infect Dis. 2021;6(3):128. doi: 10.3390/tropicalmed6030128.

537. Santos-Filho JCL, Vieira MC, Xavier IGG, Maciel ER, Rodrigues LF Jr, Curvo, et al. Quality of Life and Associated Factors in Patients with Chronic Chagas Disease. Trop Med Int Health. 2018;23(11):1213-22. doi: 10.1111/tmi.13144.

538. Díaz-Bello Z, Noya BA, Muñoz-Calderón A, Ruiz-Guevara R, Mauriello L, Colmenares C, et al. Ten-year Follow-up of the Largest Oral Chagas Disease Outbreak. Laboratory Biomarkers of Infection as Indicators of Therapeutic Failure. Acta Trop. 2021;222:106034. doi: 10.1016/j. actatropica.2021.106034.

539. Villar JC, Perez JG, Cortes OL, Riarte A, Pepper M, Marin-Neto JA, et al. Trypanocidal Drugs for Chronic Asymptomatic Trypanosoma cruzi Infection. Cochrane Database Syst Rev. 2014;2014(5):CD003463. doi: 10.1002/14651858.CD003463.pub2.

540. Coura JR, Borges-Pereira J. Chronic phase of Chagas Disease: Why Should it be Treated? A Comprehensive Review. Mem Inst Oswaldo Cruz. 2011;106(6):641-5. doi: 10.1590/s0074-02762011000600001.

541. Torrico F, Gascon J, Ortiz L, Alonso-Vega C, Pinazo MJ, Schijman A, et al. Treatment of Adult Chronic Indeterminate Chagas Disease with Benznidazole and Three E1224 Dosing Regimens: A Proof-of-concept, Randomised, Placebo-controlled Trial. Lancet Infect Dis. 2018;18(4):419-30. doi: 10.1016/S1473-3099(17)30538-8.

542. Morillo CA, Waskin H, Sosa-Estani S, Bangher MC, Cuneo C, Milesi R, et al. Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. cruzi Carriers: The STOP-CHAGAS Trial. J Am Coll Cardiol. 2017;69(8):939-47. doi: 10.1016/j.jacc.2016.12.023.

543. Maguire BJ, Dahal P, Rashan S, Ngu R, Boon A, Forsyth C, et al. The Chagas Disease Study Landscape: A Systematic Review of Clinical and Observational Antiparasitic Treatment Studies to Assess the Potential for Establishing an Individual Participant-level Data Platform. PLoS Negl Trop Dis. 2021;15(8):e0009697. doi: 10.1371/journal.pntd.0009697.

544. Dias JC, Coura JR, Yasuda MA. The Present Situation, Challenges, and Perspectives Regarding the Production and Utilization of Effective Drugs Against Human Chagas Disease. Rev Soc Bras Med Trop. 2014;47(1):123-5. doi: 10.1590/0037-8682-0248-2013.

545. Yoshioka K, Manne-Goehler J, Maguire JH, Reich MR. Access to Chagas Disease Treatment in the United States After the Regulatory Approval of Benznidazole. PLoS Negl Trop Dis. 2020;14(6):e0008398. doi: 10.1371/journal.pntd.0008398.

546. Ciapponi A, Barreira F, Perelli L, Bardach A, Gascón J, Molina I, et al. Fixed vs Adjusted-dose Benznidazole for Adults with Chronic Chagas Disease without Cardiomyopathy: A Systematic Review and Meta-analysis. PLoS Negl Trop Dis. 2020;14(8):e0008529. doi: 10.1371/journal.pntd.0008529.

547. Cafferata ML, Toscani MA, Althabe F, Belizán JM, Bergel E, Berrueta M, et al. Short-course Benznidazole Treatment to Reduce Trypanosoma cruzi Parasitic Load in Women of Reproductive Age (BETTY): A Non-inferiority Randomized Controlled Trial Study Protocol. Reprod Health. 2020;17(1):128. doi: 10.1186/s12978-020-00972-1.

548. Molina-Morant D, Fernández ML, Bosch-Nicolau P, Sulleiro E, Bangher M, Salvador F, et al. Efficacy and Safety Assessment of Different Dosage of Benznidazol for the Treatment of Chagas Disease in Chronic Phase in Adults (MULTIBENZ Study): Study Protocol for a Multicenter Randomized Phase II Non-inferiority Clinical Trial. Trials. 2020;21(1):328. doi: 10.1186/s13063-020-4226-2.
549. Alonso-Vega C, Urbina JA, Sanz S, Pinazo MJ, Pinto JJ, Gonzalez VR, et al. New Chemotherapy Regimens and Biomarkers for Chagas Disease: The Rationale and Design of the TESEO Study, an Open-label, Randomised, Prospective, Phase-2 clinical Trial in the Plurinational State of Bolivia. BMJ Open. 2021;11(12):e052897. doi: 10.1136/bmjopen-2021-052897.

550. Fonseca KDS, Perin L, Paiva NCN, Silva BC, Duarte THC, Marques FS, et al. Benznidazole Treatment: Time- and Dose-dependence Varies with the Trypanosoma cruzi Strain. Pathogens. 2021;10(6):729. doi: 10.3390/pathogens10060729.

551. Brasil. Ministério da Saúde. Normas de Segurança para Infecções Acidentais com o Trypanosoma cruzi, Agente Causador da Doença de Chagas. Rev Patol Trop. 1997;26(1):129-30. doi: 10.5216/rpt.v26i1.17376.

552. Chambela MDC, Mediano MFF, Carneiro FM, Ferreira RR, Waghabi MC, Mendes VG, et al. Impact of Pharmaceutical Care on the Quality of Life of Patients with Heart Failure Due to Chronic Chagas Disease: Randomized Clinical Trial. Br J Clin Pharmacol. 2020;86(1):143-54. doi: 10.1111/bcp.14152.

553. Altcheh J, Corral R, Biancardi MA, Freilij H. Anti-F2/3 Antibodies as Cure Marker in Children with Congenital Trypanosoma cruzi Infection. Medicina (B Aires). 2003;63(1):37-40.

554. Abbott A, Montgomery SP, Chancey RJ. Characteristics and Adverse Events of Patients for Whom Nifurtimox was Released Through CDC-Sponsored Investigational New Drug Program for Treatment of Chagas Disease - United States, 2001-2021. MMWR Morb Mortal Wkly Rep. 2022;71(10):371-4. doi: 10.15585/mmwr.mm7110a2.

555. Bruneto EG, Fernandes-Silva MM, Toledo-Cornell C, Martins S, Ferreira JMB, Corrêa VR, et al. Case-fatality from Orally-transmitted Acute Chagas Disease: A Systematic Review and Meta-analysis. Clin Infect Dis. 2021;72(6):1084-92. doi: 10.1093/cid/ciaa1148.

556. Pinto AY, Valente VC, Coura JR, Valente SA, Junqueira AC, Santos LC, et al. Clinical Follow-up of Responses to Treatment with Benznidazole in Amazon: A Cohort Study of Acute Chagas Disease. PLoS One. 2013;8(5):e64450. doi: 10.1371/journal.pone.0064450.

557. Rassi A, Luquetti AO. Specific Treatment for Trypanosoma cruzi Infection (Chagas Disease) In: Tyler KM, Miles MA, editors. American Trypanosomiasis. World Class Parasites. Boston: Kluwer Academic Publishers; 2003.

558. Luquetti AO. Etiological treatment for Chagas disease—The National Health Foundation of Brazil. Parasitol Today 1997;13(4):127-8. doi: 10.1016/S0169-4758(97)01018-1.

559. Bern C, Martin DL, Gilman RH. Acute and Congenital Chagas Disease. Adv Parasitol. 2011;75:19-47. doi: 10.1016/B978-0-12-385863-4.00002-2.

560. Bastos CJ, Aras R, Mota G, Reis F, Dias JP, Jesus RS, et al. Clinical Outcomes of Thirteen Patients with Acute Chagas Disease Acquired through Oral Transmission from Two Urban Outbreaks in Northeastern Brazil. PLoS Negl Trop Dis. 2010;4(6):e711. doi: 10.1371/journal.pntd.0000711.

561. Pinto AY, Ferreira AG Jr, Valente VC, Harada GS, Valente SA. Urban Outbreak of Acute Chagas Disease in Amazon Region of Brazil: Four-year Follow-up After Treatment with Benznidazole. Rev Panam Salud Publica. 2009;25(1):77-83. doi: 10.1590/s1020-49892009000100012.

562. Russomando G, Tomassone MM, Guillen I, Acosta N, Vera N, Almiron M, et al. Treatment of Congenital Chagas' Disease Diagnosed and Followed up by the Polymerase Chain Reaction. Am J Trop Med Hyg. 1998;59(3):487-91. doi: 10.4269/ajtmh.1998.59.487.

563. Cancado JR. Long Term Evaluation of Etiological Treatment of Chagas Disease with Benznidazole. Rev Inst Med Trop Sao Paulo. 2002;44(1):29-37.

564. Inglessis I, Carrasco HA, Añez N, Fuenmayor C, Parada H, Pacheco JA, et al. Clinical, Parasitological and Histopathologic Follow-up Studies of Acute Chagas Patients Treated with Benznidazole. Arch Inst Cardiol Mex. 1998;68(5):405-10.

565. Parada H, Carrasco HA, Añez N, Fuenmayor C, Inglessis I. Cardiac Involvement is a Constant Finding in Acute Chagas' Disease: a Clinical, Parasitological and Histopathological Study. Int J Cardiol. 1997;60(1):49-54. doi: 10.1016/s0167-5273(97)02952-5.

566. Blanco SB, Segura EL, Cura EN, Chuit R, Tulián L, Flores I, et al. Congenital Transmission of Trypanosoma cruzi: An Operational Outline for Detecting and Treating Infected Infants in North-western Argentina. Trop Med Int Health. 2000;5(4):293-301. doi: 10.1046/j.1365-3156.2000.00548.x.

567. Andrade AL, Martelli CM, Oliveira RM, Silva SA, Aires AL, Soussumi LM, et al. Short Report: Benznidazole Efficacy Among Trypanosoma cruzi-Infected Adolescents After a Six-year Follow-up. Am J Trop Med Hyg. 2004;71(5):594-7.

568. Silveira CA, Castillo E, Castro C. Evaluation of an Specific Treatment for Trypanosoma cruzi in Children, in the Evolution of the Indeterminate Phase. Rev Soc Bras Med Trop. 2000;33(2):191-6. doi: 10.1590/s0037-86822000000200006.

569. Álvarez MG, Vigliano C, Lococo B, Bertocchi G, Viotti R. Prevention of Congenital Chagas Disease by Benznidazole Treatment in Reproductive-age Women. An Observational Study. Acta Trop. 2017;174:149-52. doi: 10.1016/j.actatropica.2017.07.004.

570. Murcia L, Simón M, Carrilero B, Roig M, Segovia M. Treatment of Infected Women of Childbearing Age Prevents Congenital Trypanosoma cruzi Infection by Eliminating the Parasitemia Detected by PCR. J Infect Dis. 2017;215(9):1452-8. doi: 10.1093/infdis/jix087.

571. Moscatelli G, Moroni S, García-Bournissen F, Ballering G, Bisio M, Freilij H, et al. Prevention of Congenital Chagas Through Treatment of Girls and Women of Childbearing age. Mem Inst Oswaldo Cruz. 2015;110(4):507-9. doi: 10.1590/0074-02760140347.

572. Murcia L, Carrilero B, Munoz-Davila MJ, Thomas MC, López MC, Segovia M. Risk Factors and Primary Prevention of Congenital Chagas Disease in a Nonendemic Country. Clin Infect Dis. 2013;56(4):496-502. doi: 10.1093/cid/cis910.

573. Sousa AS, Vermeij D, Parra-Henao G, Lesmo V, Fernández EF, Aruni JJC, et al. The CUIDA Chagas Project: Towards the Elimination of Congenital Transmission of Chagas Disease in Bolivia, Brazil, Colombia, and Paraguay. Rev Soc Bras Med Trop. 2022;55:e01712022. doi: 10.1590/0037-8682-0171-2021.

574. Viotti R, Vigliano C, Armenti H, Segura E. Treatment of Chronic Chagas' Disease with Benznidazole: Clinical and Serologic Evolution of Patients with Long-term Follow-up. Am Heart J. 1994;127(1):151-62. doi: 10.1016/0002-8703(94)90521-5.

575. Catalioti F, Acquatella H. Comparacion de Mortalidad Durante Seguimiento por 5 años en Sujetos con Enfermedad de Chagas Cronica con y sin Tratamiento de Benznidazol. Rev Patol Trop 1998;27(1):29-31. doi: 10.5216/rpt.v27i1.31695.

576. Suasnábar DF, Arias E, Streiger M, Piacenza M, Ingaramo M, Del Barco M, et al. Evolutive Behavior Towards Cardiomyopathy of Treated (Nifurtimox or Benznidazole) and Untreated Chronic Chagasic Patients. Rev Inst Med Trop Sao Paulo. 2000;42(2):99-109. doi: 10.1590/s0036-46652000000200007.

577. Gallerano RR, Sosa RR. Interventional Study in the Natural Evolution of Chagas Disease. Evaluation of Specific Antiparasitic Treatment. Retrospective-prospective Study of Antiparasitic Therapy. Rev Fac Cien Med Univ Nac Cordoba. 2000;57(2):135-62.

578. Rassi A, Luquetti AO. Critérios de Cura da Infecção pelo Trypanosoma cruzi na Espécie Humana. In: Coura JR, editor. Dinâmica das Doenças Infecciosas e Parasitárias. Rio de Janeiro: Guanabra Koogan; 2005.

579. Coura JR, Abreu LL, Willcox HPF, Petana W. Estudo Comparativo Controlado com Emprego de Benznidazole, Nifurtimox e Placebo, na Forma Crônica da Doença de Chagas, em uma Área de Campo com Transmissão Interrompida. I. Avaliação preliminar. Rev Soc Bras Med Trop. 1997;30(2):139-44. doi: 10.1590/S0037-86821997000200009.

580. Sartori AM, Ibrahim KY, Westphalen EVN, Braz LM, Oliveira OC Jr, Gakiya E, et al. Manifestations of Chagas Disease (American trypanosomiasis) in Patients with HIV/AIDS. Ann Trop Med Parasitol. 2007;101(1):31-50. doi: 10.1179/136485907X154629.

581. Rossi Neto JM, Finger MA, Dos Santos CC. Benznidazole as Prophylaxis for Chagas Disease Infection Reactivation in Heart Transplant Patients: A Case Series in Brazil. Trop Med Infect Dis. 2020;5(3):132. doi: 10.3390/tropicalmed5030132.
582. Salvador F, Sánchez-Montalvá A, Valerio L, Serre N, Roure S, Treviño B, et al. Immunosuppression and Chagas Disease: Experience from a Non-endemic country. Clin Microbiol Infect. 2015;21(9):854-60. doi: 10.1016/j.cmi.2015.05.033.

583. Altclas J, Sinagra A, Dictar M, Luna C, Verón MT, De Rissio AM, et al. Chagas Disease in Bone Marrow Transplantation: An Approach to Preemptive Therapy. Bone Marrow Transplant. 2005;36(2):123-9. doi: 10.1038/sj.bmt.1705006.

584. Carvalho VB, Sousa EF, Vila JH, Silva JP, Caiado MR, Araujo SR, et al. Heart Transplantation in Chagas' Disease. 10 Years After the Initial Experience. Circulation. 1996;94(8):1815-7. doi: 10.1161/01.cir.94.8.1815.

585. Kinoshita-Yanaga AT, Toledo MJ, Araújo SM, Vier BP, Gomes ML. Accidental Infection by Trypanosoma cruzi Follow-up by the Polymerase Chain Reaction: Case Report. Rev Inst Med Trop Sao Paulo. 2009;51(5):295-8. doi: 10.1590/s0036-46652009000500011.

586. Sguassero Y, Roberts KN, Harvey GB, Comandé D, Ciapponi A, Cuesta CB, et al. Course of Serological Tests in Treated Subjects with Chronic Trypanosoma cruzi Infection: A Systematic Review and Meta-analysis of Individual Participant Data. Int J Infect Dis. 2018;73:93-101. doi: 10.1016/j.ijid.2018.05.019.

587. Sguassero Y, Cuesta CB, Roberts KN, Hicks E, Comandé D, Ciapponi A, et al. Course of Chronic Trypanosoma cruzi Infection After Treatment Based on Parasitological and Serological Tests: A Systematic Review of Follow-up Studies. PLoS One. 2015;10(10):e0139363. doi: 10.1371/journal.pone.0139363.

588. Crespillo-Andújar C, Comeche B, Hamer DH, Arevalo-Rodríguez I, Alvarez-Díaz N, Zamora J, et al. Use of Benznidazole to Treat Chronic Chagas Disease: An Updated Systematic Review with a Meta-analysis. PLoS Negl Trop Dis. 2022;16(5):e0010386. doi: 10.1371/journal.pntd.0010386.

589. Holanda MT, Mediano MFF, Hasslocher-Moreno AM, Gonzaga BMS, Carvalho ACC, Ferreira RR, et al. Effects of Selenium Treatment on Cardiac Function in Chagas Heart Disease: Results from the STCC Randomized Trial. EClinicalMedicine. 2021;40:101105. doi: 10.1016/j.eclinm.2021.101105.

590. Ferreira JMBB. Pathophysiology and New Targets for Therapeutic Options in Chagas Heart Disease. Mem Inst Oswaldo Cruz. 2022;117:e210172chgsa. doi: 10.1590/0074-02760210172chgsa.

591. Barbosa AP, Cardinalli Neto A, Otaviano AP, Rocha BF, Bestetti RB. Comparison of Outcome Between Chagas Cardiomyopathy and Idiopathic Dilated Cardiomyopathy. Arq Bras Cardiol. 2011;97(6):517-25. doi: 10.1590/s0066-782x2011005000112.

592. Shen L, Ramires F, Martinez F, Bodanese LC, Echeverría LE, Gómez EA, et al. PARADIGM-HF and ATMOSPHERE Investigators and Committees. Contemporary Characteristics and Outcomes in Chagasic Heart Failure Compared With Other Nonischemic and Ischemic Cardiomyopathy. Circ Heart Fail. 2017;10(11):e004361. doi: 10.1161/CIRCHEARTFAILURE.117.004361.

593. Araujo-Jorge TC, Ferreira RR. Translational Research in Chagas Disease: Perspectives in Nutritional Therapy Emerging from Selenium Supplementation Studies as a Complementary Treatment. Mem Inst Oswaldo Cruz. 2022;117:e220001. doi: 10.1590/0074-02760220001.

594. CONSENSUS Trial Study Group. Effects of Enalapril on Mortality in Severe Congestive Heart Failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316(23):1429-35. doi: 10.1056/NEJM198706043162301.

595. Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure. N Engl J Med. 1991;325(5):293-302. doi: 10.1056/NEJM199108013250501.

596. Garg R, Yusuf S. Overview of Randomized Trials of Angiotensin-converting Enzyme Inhibitors on Mortality and Morbidity in Patients with Heart Failure. Collaborative Group on ACE Inhibitor Trials. JAMA. 1995;273(18):1450-6.

597. Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin Receptor Blockers for Heart Failure. Cochrane Database Syst Rev. 2012;2012(4):CD003040. doi: 10.1002/14651858.CD003040.pub2.

598. Khoury AM, Davila DF, Bellabarba G, Donis JH, Torres A, Lemorvan C, et al. Acute Effects of Digitalis and Enalapril on the Neurohormonal Profile of Chagasic Patients with Severe Congestive Heart Failure. Int J Cardiol. 1996;57(1):21-9. doi: 10.1016/s0167-5273(96)02776-3.

599. Roberti RR, Martinez EE, Andrade JL, Araujo VL, Brito FS, Portugal OP, et al. Chagas Cardiomyopathy and Captopril. Eur Heart J. 1992;13(7):966-70. doi: 10.1093/oxfordjournals.eurheartj.a060301.

600. Szajnbok FE, Barretto AC, Mady C, Parga Filho J, Gruppi C, Alfieri RG, et al. Beneficial Effects of Enalapril on the Diastolic Ventricular Function in Chagas Myocardiopathy. Arq Bras Cardiol. 1993;60(4):273-8.

601. Pérez-Molina JA, Molina I. Chagas Disease. Lancet. 2018;391(10115):82-94. doi: 10.1016/S0140-6736(17)31612-4.

602. Waagstein F. Beta-adrenergic Blockade in Dilated Cardiomyopathy, Ischemic Cardiomyopathy, and Other Secondary Cardiomyopathies. Heart Vessels Suppl. 1991;6:18-28. doi: 10.1007/BF01752532.

603. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334(21):1349-55. doi: 10.1056/NEJM19960523342101.

604. Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, et al. Efficacy of ☐ Blockers in Patients with Heart Failure Plus Atrial Fibrillation: An Individual-patient Data Meta-analysis. Beta-Blockers in Heart Failure Collaborative Group. Lancet. 2014;384(9961):2235-43. doi: 10.1016/S0140-6736(14)61373-8.

605. Issa VS, Amaral AF, Cruz FD, Ferreira SM, Guimarães GV, Chizzola PR, et al. Beta-Blocker Therapy and Mortality of Patients with Chagas Cardiomyopathy: A Subanalysis of the REMADHE Prospective Trial. Circ Heart Fail. 2010;3(1):82-8. doi: 10.1161/CIRCHEARTFAILURE.109.882035.

606. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709-17. doi: 10.1056/NEJM199909023411001.

607. Juurink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, et al. Rates of Hyperkalemia After Publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351(6):543-51. doi: 10.1056/NEJMoa040135.

608. Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, et al. Ivabradine and Outcomes in Chronic Heart Failure (SHIFT): A Randomised Placebo-controlled Study. Lancet. 2010;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.

609. Vamos M, Erath JW, Benz AP, Lopes RD, Hohnloser SH. Meta-Analysis of Effects of Digoxin on Survival in Patients with Atrial Fibrillation or Heart Failure: An Update. Am J Cardiol. 2019;123(1):69-74. doi: 10.1016/j.amjcard.2018.09.036.

610. Digitalis Investigation Group. The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure. N Engl J Med. 1997;336(8):525-33. doi: 10.1056/NEJM199702203360801.

611. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin Inhibition Versus Enalapril in Heart Failure. N Engl J Med. 2014;371(11):993-1004. doi: 10.1056/NEJMoa1409077.

612. Correia LC, Rassi A Jr. Paradigm-HF: A Paradigm Shift in Heart Failure Treatment? Arq Bras Cardiol. 2016;106(1):77-9. doi: 10.5935/abc.20160009.

613. Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde. Protocolo Clínico e Diretrizes Terapêuticas. Portaria n. 40, de 8 de agosto de 2019. Comissão Nacional de Incorporação de Tecnologias no SUS. Sacubitril/valsartana para o Tratamento de Pacientes Adultos com Insuficiência Cardíaca Crônica Sintomática (NYHA classe II-IV) com Fração de Ejeção Reduzida. Brasília: Ministério da Saúde; 2019.
# Guidelines

614. Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, et al. PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019;381(17):1609-20. doi: 10.1056/NEJMoa1908655.

615. Pfeffer MA, Claggett B, Lewis EF, Granger CB, Køber L, Maggioni AP, et al. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction. N Engl J Med. 2021;385(20):1845-55. doi: 10.1056/NEJMoa2104508.

616. Figueiredo CS, Melo RMV, Viana TT, Jesus AGQ, Silva TC, Silva VM, et al. Clinical and Echocardiographic Characteristics After Six Months of Sacubitril/ valsartan in Chagas Heart Disease - A Case Series. Br J Clin Pharmacol. 2022;88(2):429-36. doi: 10.1111/bcp.14978.

617. Silva RMFL, Garcia PVC, Ikematu EKI. Clinical Representativeness of the PARADIGM-HF Study in an Outpatient Cohort of Patients with Heart Failure, Including Chagas Disease, Treated According to Guideline-directed Medical Therapy: Prospective Study, in a Single Center in Brazil. Cardiol Angiol. 2020;9(3):38-45. doi: 10.9734/ca/2020/v9i330138.

618. Ramires FJA, Martinez F, Gómez EA, Demacq C, Gimpelewicz CR, Rouleau JL, et al. Post Hoc Analyses of SHIFT and PARADIGM-HF Highlight the Importance of Chronic Chagas' Cardiomyopathy Comment on: "Safety Profile and Efficacy of Ivabradine in Heart Failure Due to Chagas Heart Disease: A Post Hoc Analysis of the SHIFT Trial" by Bocchi et al. ESC Heart Fail. 2018;5(6):1069-71. doi: 10.1002/ehf2.12355.

619. Clar C, Gill JA, Court R, Waugh N. Systematic Review of SGLT2 Receptor Inhibitors in Dual or Triple Therapy in Type 2 Diabetes. BMJ Open. 2012;2(5):e001007. doi: 10.1136/bmjopen-2012-001007.

620. Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, et al. Long-term Efficacy of Dapagliflozin in Patients with Type 2 Diabetes Mellitus Receiving High Doses of Insulin: A Randomized Trial. Dapagliflozin 006 Study Group. Ann Intern Med. 2012;156(6):405-15. doi: 10.7326/0003-4819-156-6-201203200-00003.

621. Rosenstock J, Jelaska A, Frappin G, Salsali A, Kim G, Woerle HJ, et al. EMPA-REG MDI Trial Investigators. Improved Glucose Control with Weight Loss, Lower Insulin Doses, and no Increased Hypoglycemia with Empagliflozin Added to Titrated Multiple Daily Injections of Insulin in Obese Inadequately Controlled Type 2 Diabetes. Diabetes Care. 2014;37(7):1815-23. doi: 10.2337/dc13-3055.

622. Nauck MA, Del Prato S, Meier JJ, Durán-García S, Rohwedder K, Elze M, et al. Dapagliflozin Versus Glipizide as Add-on Therapy in Patients with type 2 Diabetes who have Inadequate Glycemic Control with Metformin: A Randomized, 52-Week, Double-blind, Active-controlled Noninferiority Trial. Diabetes Care. 2011;34(9):2015-22. doi: 10.2337/dc11-0606.

623. Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, et al. Canagliflozin Compared with Sitagliptin for Patients with Type 2 Diabetes Who do not have Adequate Glycemic Control with Metformin Plus Sulfonylurea: A 52-week Randomized Trial. Diabetes Care. 2013;36(9):2508-15. doi: 10.2337/dc12-2491.

624. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-57. doi: 10.1056/NEJMoa1812389.

625. Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020;383(15):1425-35. doi: 10.1056/NEJMoa2004967.

626. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. doi: 10.1056/NEJMoa1504720.

627. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi: 10.1056/NEJMoa1911303.

628. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-24. doi: 10.1056/NEJMoa2022190.

629. Butt JH, Nicolau JC, Verma S, Docherty KF, Petrie MC, Inzucchi SE, et al. Efficacy and Safety of Dapagliflozin According to Aetiology in Heart Failure with Reduced Ejection Fraction: Insights from the DAPA-HF Trial. Eur J Heart Fail. 2021;23(4):601-13. doi: 10.1002/ejhf.2124.

630. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-61. doi: 10.1056/NEJMoa2107038.

631. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart Disease and Stroke Statistics--2015 Update: A Report from the American Heart Association. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2015;131(4):e29-322. doi: 10.1161/CIR.0000000000000152.

632. Abuhab A, Trindade E, Aulicino GB, Fujii S, Bocchi EA, Bacal F. Chagas' Cardiomyopathy: the Economic Burden of an Expensive and Neglected Disease. Int J Cardiol. 2013;168(3):2375-80. doi: 10.1016/j.ijcard.2013.01.262.

633. International Society of Heart and Lung Transplantation: Adult Heart Transplantation Statistics. J Heart Lung Transplant. 2016;35(10):1149-205.

634. Mehra MR, Kobashigawa J, Starling R, Russell S, Uber PA, Parameshwar J, et al. Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates--2006. J Heart Lung Transplant. 2006;25(9):1024-42. doi: 10.1016/j.healun.2006.06.008.

635. Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, et al. International Society of Heart and Lung Transplantation Guidelines. The International Society of Heart and Lung Transplantation Guidelines for the Care of Heart Transplant Recipients. J Heart Lung Transplant. 2010;29(8):914-56. doi: 10.1016/j.healun.2010.05.034.

636. Khush KK, Cherikh WS, Chambers DC, Harhay MO, Hayes D Jr, Hsich E, et al. International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth Adult Heart Transplantation Report - 2019; Focus Theme: Donor and Recipient Size Match. J Heart Lung Transplant. 2019;38(10):1056-66. doi: 10.1016/j.healun.2019.08.004.

637. Briasoulis A, Inampudi C, Pala M, Asleh R, Alvarez P, Bhama J. Induction Immunosuppressive Therapy in Cardiac Transplantation: A Systematic Review and Meta-analysis. Heart Fail Rev. 2018;23(5):641-9. doi: 10.1007/s10741-018-9691-2.

638. Bacal F, Silva CP, Bocchi EA, Pires PV, Moreira LF, Issa VS, et al. Mychophenolate Mofetil Increased Chagas Disease Reactivation in Heart Transplanted Patients: Comparison Between Two Different Protocols. Am J Transplant. 2005;5(8):2017-21. doi: 10.1111/j.1600-6143.2005.00975.x.

639. Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Heart Rejection. J Heart Lung Transplant. 2005;24(11):1710-20. doi: 10.1016/j.healun.2005.03.019.

640. Bocchi EA, Fiorelli A. The Paradox of Survival Results After Heart Transplantation for Cardiomyopathy Caused by Trypanosoma cruzi. First Guidelines Group for Heart Transplantation of the Brazilian Society of Cardiology. Ann Thorac Surg. 2001;71(6):1833-8. doi: 10.1016/s0003-4975(01)02587-5.

641. Bocchi EA, Fiorelli A. The Brazilian Experience with Heart Transplantation: A Multicenter Report. J Heart Lung Transplant. 2001;20(6):637-45. doi: 10.1016/s1053-2498(00)00235-7.

642. Bestetti RB, Theodoropoulos TA. A Systematic Review of Studies on Heart Transplantation for Patients with End-stage Chagas' Heart Disease. J Card Fail. 2009;15(3):249-55. doi: 10.1016/j.cardfail.2008.10.023.

643. Fiorelli AI, Santos RH, Oliveira JL Jr, Lourenço-Filho DD, Dias RR, Oliveira AS, et al. Heart Transplantation in 107 Cases of Chagas' Disease. Transplant Proc. 2011;43(1):220-4. doi: 10.1016/j.transproceed.2010.12.046.
644. Souza MM, Franco M, Almeida DR, Diniz RV, Mortara RA, Silva S, et al. Comparative Histopathology of Endomyocardial Biopsies in Chagasic and Non-chagasic Heart Transplant Recipients. J Heart Lung Transplant. 2001;20(5):534-43. doi: 10.1016/s1053-2498(00)00320-x.

645. Campos SV, Strabelli TM, Amato Neto V, Silva CP, Bacal F, Bocchi EA, et al. Risk Factors for Chagas' Disease Reactivation After Heart Transplantation. J Heart Lung Transplant. 2008;27(6):597-602. doi: 10.1016/j.healun.2008.02.017.

646. Godoy HL, Guerra CM, Viegas RF, Dinis RZ, Branco JN, Neto VA, et al. Infections in Heart Transplant Recipients in Brazil: The Challenge of Chagas' Disease. J Heart Lung Transplant. 2010;29(3):286-90. doi: 10.1016/j.healun.2009.08.006.

647. Gray EB, La Hoz RM, Green JS, Vikram HR, Benedict T, Rivera H, et al. Reactivation of Chagas Disease Among Heart Transplant Recipients in the United States, 2012-2016. Transpl Infect Dis. 2018;20(6):e12996. doi: 10.1111/tid.12996.

648. Chin-Hong PV, Schwartz BS, Bern C, Montgomery SP, Kontak S, Kubak B, et al. Screening and Treatment of Chagas Disease in Organ Transplant Recipients in the United States: Recommendations from the Chagas in Transplant Working Group. Am J Transplant. 2011;11(4):672-80. doi: 10.1111/j.1600-6143.2011.03444.x.

649. Kransdorf EP, Zakowski PC, Kobashigawa JA. Chagas Disease in Solid Organ and Heart Transplantation. Curr Opin Infect Dis. 2014;27(5):418-24. doi: 10.1097/QCO.0000000000000088.

650. La Hoz RM, Morris MI. Tissue and Blood Protozoa Including Toxoplasmosis, Chagas Disease, Leishmaniasis, Babesia, Acanthamoeba, Balamuthia, and Naegleria in Solid Organ Transplant Recipients-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13546. doi: 10.1111/ctr.13546.

651. Pierrotti LC, Carvalho NB, Amorin JP, Pascual J, Kotton CN, López-Vélez R. Chagas Disease Recommendations for Solid-organ Transplant Recipients and Donors. Transplantation. 2018;102(2):1-7. doi: 10.1097/TP.00000000000002019.

652. Camargos S, Moreira MDV, Portela DMMC, Lira JPI, Modesto FVS, Menezes GMM, et al. CNS Chagoma: Reactivation in an Immunosuppressed Patient. Neurology. 2017;88(6):605-6. doi: 10.1212/WNL.00000000000003600.

653. Moreira MDCV, Cunha-Melo JR. Chagas Disease Infection Reactivation After Heart Transplant. Trop Med Infect Dis. 2020;5(3):106. doi: 10.3390/tropicalmed5030106.

654. Moreira MC, Castilho FM, Braulio R, Andrade GFMP, Cunha-Melo JR. Heart Transplantation for Chagas Cardiomyopathy. Int. J. Cardiovasc. Sci. 2020;33(6):697-704. doi: 10.36660/ijcs.20200248.

655. Radisic MV, Repetto SA. American Trypanosomiasis (Chagas Disease) in Solid Organ Transplantation. Transpl Infect Dis. 2020;22(6):e13429. doi: 10.1111/tid.13429.

656. Maldonado C, Albano S, Vettorazzi L, Salomone O, Zlocowski JC, Abiega C, et al. Using Polymerase Chain Reaction in Early Diagnosis of Re-activated Trypanosoma Cruzi Infection After Heart Transplantation. J Heart Lung Transplant. 2004;23(12):1345-8. doi: 10.1016/j.healun.2003.09.027.

657. Qvarnstrom Y, Schijman AG, Veron V, Aznar C, Steurer F, Silva AJ. Sensitive and Specific Detection of Trypanosoma cruzi DNA in Clinical Specimens Using a Multi-target Real-time PCR Approach. PLoS Negl Trop Dis. 2012;6(7):e1689. doi: 10.1371/journal.pntd.0001689.

658. Moreira OC, Ramírez JD, Velázquez E, Melo MF, Lima-Ferreira C, Guhl F, et al. Towards the Establishment of a Consensus Real-time qPCR to Monitor Trypanosoma cruzi Parasitemia in Patients with chronic Chagas Disease Cardiomyopathy: A Substudy from the BENEFIT Trial. Acta Trop. 2013;125(1):23-31. doi: 10.1016/j.actatropica.2012.08.020.

659. Ortega AME, López ZRA, Pérez RH, Millón CMF, Martín AD, Palomo YC, et al. Kidney Failure After Heart Transplantation. Transplant Proc. 2010;42(8):3193-5. doi: 10.1016/j.transproceed.2010.05.049.

660. Vieira JL, Sobral MGV, Macedo FY, Florêncio RS, Almeida GPL, Vasconcelos GG, et al. Long-term Survival Following Heart Transplantation for Chagas Versus Non-Chagas Cardiomyopathy: A Single-center Experience in Northeastern Brazil Over 2 Decades. Transplant Direct. 2022;8(7):e1349. doi: 10.1097/TXD.0000000000001349.

661. Ayub-Ferreira SM, Souza Neto JD, Almeida DR, Biselli B, Avila MS, Colafranceschi AS, et al. Diretriz de Assistência Circulatória Mecânica da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2016;107(2):1-33. doi: 10.5935/abc.20160128.

662. Bocchi EA, Vieira ML, Fiorelli A, Hayashida S, Mayzato M, Leirner A, et al. Hemodynamic and Neurohormonal Profile During Assisted Circulation with Heterotopic Artificial Ventricle Followed by Heart Transplantation. Arq Bras Cardiol. 1994;62(1):23-7.

663. Moreira LF, Galantier J, Benício A, Leirner AA, Cestari IA, Stolf NA. Left Ventricular Circulatory Support as Bridge to Heart Transplantation in Chagas' Disease Cardiomyopathy. Artif Organs. 2007;31(4):253-8. doi: 10.1111/j.1525-1594.2007.00372.x.

664. Kransdorf EP, Czer LS, Luthringer DJ, Patel JK, Montgomery SP, Velleca A, et al. Heart Transplantation for Chagas Cardiomyopathy in the United States. Am J Transplant. 2013;13(12):3262-8. doi: 10.1111/ajt.12507.

665. Ruzza A, Czer LS, Robertis M, Luthringer D, Moriguchi J, Kobashigawa J, et al. Total Artificial Heart as Bridge to Heart Transplantation in Chagas Cardiomyopathy: Case Report. Transplant Proc. 2016;48(1):279-81. doi: 10.1016/j.transproceed.2015.12.017.

666. Persoon MC, Manintveld OC, Mollema FPN, Van Hellemond JJ. An Unusual Case of Congestive Heart Failure in the Netherlands. JMM Case Rep. 2018;5(4):e005142. doi: 10.1099/jmmcr.0.005142.

667. Atik FA, Cunha CR, Chaves RB, Ulhoa MB, Barzilai VS. Left Ventricular Assist Device as a Bridge to Candidacy in End-stage Chagas Cardiomyopathy. Arq Bras Cardiol. 2018;111(1):112-4. doi: 10.5935/abc.20180095.

668. Hidalgo R, Martí-Carvajal AJ, Kwong JS, Simancas-Racines D, Nicola S. Pharmacological Interventions for Treating Heart Failure in Patients with Chagas Cardiomyopathy. Cochrane Database Syst Rev. 2012;11:CD009077. doi: 10.1002/14651858.CD009077.pub2.

669. Cedraz SS, Silva PC, Minowa RK, Aragão JF, Silva DV, Morillo C, et al. Electrophysiological Characteristics of Chagas Disease. Einstein (São Paulo). 2013;11(3):291-5. doi: 10.1590/s1679-45082013000300006.

670. Pimenta J, Miranda M, Pereira CB. Electrophysiologic Findings in Long-term Asymptomatic Chagasic Individuals. Am Heart J. 1983;106(2):374-80. doi: 10.1016/0002-8703(83)90206-5.

671. Paola AA, Horowitz LN, Miyamoto MH, Pinheiro R, Ferreira DF, Terzian AB, et al. Angiographic and Electrophysiologic Substrates of Ventricular Tachycardia in Chronic Chagasic Myocarditis. Am J Cardiol. 1990;65(5):360-3. doi: 10.1016/0002-9149(90)90302-h.

672. Rassi A Jr, Rassi AG, Rassi SG, Rassi L Jr, Rassi A. Ventricular Arrhythmia in Chagas Disease. Diagnostic, Prognostic, and Therapeutic Features. Arq Bras Cardiol. 1995;65(4):377-87.

673. Guerrero L, Carrasco H, Parada H, Molina C, Chuecos R. Ventricular Mechanics and Cardiac Arrhythmias in Patients with Chagasic and Primary Dilated Cardiomyopathy. Echo-Electrocardiographic Follow-up. Arq Bras Cardiol. 1991;56(6):465-9.

674. Samuel J, Oliveira M, Araujo RRC, Navarro MA, Muccillo G. Am J Cardiol. Cardiac Thrombosis and Thromboembolism in Chronic Chagas' Heart Disease. Am J Cardiol. 1983;52(1):147-51. doi: 10.1016/0002-9149(83)90085-1.

675. Freitas HF, Chizzola PR, Paes AT, Lima AC, Mansur AJ. Risk Stratification in a Brazilian Hospital-based Cohort of 1220 Outpatients with Heart Failure: Role of Chagas' Heart Disease. Int J Cardiol. 2005;102(2):239-47. doi: 10.1016/j.ijcard.2004.05.025.

676. Cooper HA, Dries DL, Davis CE, Shen YL, Domanski MJ. Diuretics and Risk of Arrhythmic Death in Patients with Left Ventricular Dysfunction. Circulation. 1999;100(12):1311-5. doi: 10.1161/01.cir.100.12.1311.