Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models.

Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

Cardiac and Liver Fibrosis Assessed by Multiparametric MRI in Patients with Fontan Circulation.

The abnormal hemodynamics in Fontan circulation due to persistently increased systemic venous pressure results in hepatic venous congestion and Fontan-associated liver disease. Combined assessment of cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in this context have not been fully explored. To evaluate cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in patients who have undergone Fontan procedures. Thirty-eight patients and 23 controls underwent cardiac and liver MRI examinations in a 3.0-T scanner. Mann-Whitney, Fisher exact test, and Spearman's correlation were applied to evaluate myocardial volumes, function, native cardiac and liver T1 mapping, ECVs and liver stiffness. The mean native cardiac T1 value (p = 0.018), cardiac ECV (p < 0.001), liver native T1 (p < 0.001), liver ECV (p < 0.001), and liver stiffness (p < 0.001) were higher in patients than controls. The indexed end-diastolic volume (EDVi) correlated with the myocardial ECV (r = 0.356; p = 0.033), native liver T1 (r = 0.571; p < 0.001), and with liver stiffness (r = 0.391; p = 0.015). In addition, liver stiffness correlated with liver ECV (r = 0.361; p = 0.031) and native liver T1 (r = 0.458; p = 0.004). An association between cardiac remodeling and cardiac and liver fibrosis were found in this population. The usefulness of MRI to follow cardiac and liver involvement in these patients is critical to improve treatment strategies and to prevent the need for combined liver and heart transplantation.

Effect of an exercise-based cardiac rehabilitation program on quality of life of patients with chronic Chagas cardiomyopathy: results from the PEACH randomized clinical trial.

To investigate the effect of an exercise-based cardiac rehabilitation program on the quality of life (QoL) of patients with chronic Chagas cardiomyopathy (CCC). PEACH study was a single-center, superiority randomized clinical trial of exercise training versus no exercise (control). The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction < 45%, without or with HF symptoms (CCC stages B2 or C, respectively). QoL was assessed at baseline, after three months, and at the end of six months of follow-up using the SF-36 questionnaire. Patients randomized for the exercise group (n = 15) performed exercise training (aerobic, strength and stretching exercises) for 60 min, three times a week, during six months. Patients in the control group (n = 15) were not provided with a formal exercise prescription. Both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of exercise training on QoL, considering the interaction term (group × time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using linear mixed models. Models were fitted adjusting for each respective baseline QoL value. There were significant improvements in physical functioning (ß = + 10.7; p = 0.02), role limitations due to physical problems (ß = + 25.0; p = 0.01), and social functioning (ß = + 19.2; p < 0.01) scales during the first three months in the exercise compared to the control group. No significant differences were observed between groups after six months. Exercise-based cardiac rehabilitation provided short-term improvements in the physical and mental aspects of QoL of patients with CCC.Trial registration: ClinicalTrials.gov Identifier: NCT02517632; August 7, 2015.

The rise of home death in the COVID-19 pandemic: a population-based study of death certificate data for adults from 32 countries, 2012-2021.

Background: During the coronavirus 2019 disease (COVID-19) pandemic, health systems had to respond to the needs of COVID-19 patients, while caring for patients with other life-threatening conditions. Pandemics, such as the COVID-19 pandemic, stir global health and mortality patterns. This is likely to include trends in dying places. In this paper, we examine trends in place of death for adults in 32 countries, comparing the initial COVID-19 pandemic years (2020-2021) with the eight years before the pandemic (2012-2019). Methods: Data on place of death for all adults (18 years and over) that died from 1 January 2012 to 31 December 2021 were requested (47 countries approached, 32 included). The classification of place of death varied widely between countries. "Home" was the most common category, the remaining category groups comprised "hospital or health institution", "other defined", and "ill-defined". We analysed place of death data in an aggregate form, by sex, age group, and selected underlying causes of death (cancer, dementia, and COVID-19). Findings: The study included 100.7 million people (51.5% male, 68.0% with ≥70 years), 20.4% died from cancer and 5.8% from dementia; 30.8% of deaths took place at home. The percentage of home deaths rose from 30.1% in 2012-2013 to 30.9% in 2018-2019 and further to 32.2% in the pandemic (2020-2021). Home deaths increased during the pandemic in 23 countries. In most countries the rise was greater in women and cancer; age differences were not consistent. Interpretation: Our study shows that there was a rise in home deaths during the pandemic, but with variability across countries, sex, age, and causes of death. The sex difference observed in most countries may have several explanations, including more engagement of women in discussions about end of life care planning and hospital admission avoidance. A higher rise of home deaths among people dying of cancer may be explained by the more predictable disease trajectory compared to non-malignant conditions, as well as earlier and better integrated palliative care. Funding: This work is part of the EOLinPLACE Project, which has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 948609).

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

EOLinPLACE: an international research project to reform the way dying places are classified and understood.

Background: Whenever possible, a person should die where they feel it is the right place to be. There is substantial global variation in home death percentages but it is unclear whether these differences reflect preferences, and there are major limitations in how the place of death is classified and compared across countries. Objectives: EOLinPLACE is an international interdisciplinary research project funded by the European Research Council aiming to create a solid base for a ground-breaking international classification tool that will enable the mapping of preferred and actual places towards death. Design: Mixed-methods observational research. Methods and analysis: We combine classic methods of developing health classifications with a bottom-up participatory research approach, working with international organizations representing patients and informal carers [International Alliance of Patients' Organizations (IAPO) and Eurocarers]. First, we will conduct an international comparative analysis of existing classification systems and routinely collected death certificate data on place of death. Secondly, we will conduct a mixed-methods study (ethnography followed by longitudinal quantitative study) in four countries (the Netherlands, Portugal, Uganda and the United States), to compare the preferences and experiences of patients with life-threatening conditions and their families. Thirdly, based on the generated evidence, we will build a contemporary classification of dying places; assess its content validity through focus groups with patients, carers and other stakeholders; and evaluate it in a psychometric study to examine construct validity, reliability, responsiveness, data quality and interpretability. Ethics: Approved by the ethics committee of the University of Coimbra, Faculty of Medicine (CE-068-2022) and committees in each of the participating countries. Discussion: The findings will provide a deeper understanding of the diversity in individual end-of-life pathways. They will enable key developments such as measurement of progress towards achievement of preferences when care can be planned. The project will open new directions in how to care for the dying. Trial registration: Research Registry UIN 9213.

Patient and Family Preferences About Place of End-of-Life Care and Death: An Umbrella Review.

CONTEXT: The place where people are cared towards the end of their life and die is a complex phenomenon, requiring a deeper understanding. Honoring preferences is critical for the delivery of high-quality care. OBJECTIVES: In this umbrella review we examine and synthesize the evidence regarding preferences about place of end-of-life care and death of patients with life-threatening illnesses and their families. METHODS: Following the Joanna Briggs Institute methodology, we conducted a comprehensive search for systematic reviews in PsycINFO, MEDLINE, EMBASE, CINAHL, Epistemonikos, and PROSPERO without language restrictions. RESULTS: The search identified 15 reviews (10 high-quality, three with meta-analysis), covering 229 nonoverlapping primary studies. Home is the most preferred place of end-of-life care for both patients (11%-89%) and family members (23%-84%). It is also the most preferred place of death (patient estimates from two meta-analyses: 51%-55%). Hospitals and hospice/palliative care facilities are preferred by substantial minorities. Reasons and factors affecting preferences include illness-related, individual, and environmental. Differences between preferred places of care and death are underexplored and the evidence remains inconclusive about changes over time. Congruence between preferred and actual place of death ranges 21%-100%, is higher in studies since 2004 and a meta-analysis shows noncancer patients are at higher risk of incongruence than cancer patients (OR 1.23, 95% CI: 1.01-1.49, I2 = 62%). CONCLUSION: These findings are a crucial starting point to address gaps and enhance strategies to align care with patient and family preferences. To accurately identify patient and family preferences is an important opportunity to change their lives positively.

Chagas disease.

Chagas disease persists as a global public health problem due to the high morbidity and mortality burden. Despite the possibility of a cure and advances in transmission control, epidemiological transformations, such as urbanisation and globalisation, and the emerging importance of oral and vertical transmission mean that Chagas disease should be considered an emerging disease, with new cases occurring worldwide. Important barriers to diagnosis, treatment, and care remain, resulting in repressed numbers of reported cases, which in turn leads to inadequate public policies. The validation of new diagnostic tools and treatment options is needed, as existing tools pose serious limitations to access to health care. Integrated models of surveillance, with community and intersectional participation, embedded in the concept of One Health, are essential for control. In addition, mitigation strategies for the main social determinants of health, including difficulties imposed by migration, are important to improve access to comprehensive health care in a globalised scenario.

Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

Inspiratory Muscle Strength in Chagas Cardiomyopathy: A Systematic Scoping Review.

The increase in inflammatory markers associated with persistent chronic fibrosing myocarditis, a characteristic of chronic Chagas disease, can result in a reduction in inspiratory muscle strength (IMS) in Chagas cardiomyopathy (CC). However, literature in this field is still scarce. This review aimed to map and summarize the evidence regarding IMS in patients with CC. The inclusion criteria included reports with adult participants with a CC diagnosis, with or without heart failure (HF). The core concept examined was the maximum inspiratory pressure evaluated in the untrained and trained groups in the pre-training period. The context was open, including but not limited to hospitals and health centers. Two authors independently identified eligible studies and extracted the data. Descriptive synthesis was used as the primary strategy for analyzing the results. Nine studies (five clinical trials, three cross-sectional, and one cohort) were included. The CC classification differed among the studies, with no mention of HF in five and no CC staging specification in six. IMS was assessed using a manovacuometer, and only six studies analyzed and interpreted the data concerning the predicted values. The CC population with HF appeared to have impaired IMS. All studies involved only Brazilian volunteers. In conclusion, randomized clinical trials evaluating IMS and the effects of inspiratory muscle training need to be conducted to better understand the prevalence and risk of inspiratory muscle weakness in the CC population, as well as the effects of training. Such studies should be conducted at different stages of CC in different populations and countries.

How Cardiac Fibrosis Assessed via T1 Mapping Is Associated with Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

(1) Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Although cardiovascular and NAFLD risk factors overlap, an independent association between these conditions may exist. Hepatic and cardiac fibrosis are important markers of mortality, but the correlation between these markers in patients with NAFLD has not been well studied. Our main objective was to determine the degree of myocardial fibrosis in patients with NAFLD and its correlation with the severity of liver fibrosis. (2) Methods: In this cross-sectional study, patients with NAFLD were allocated to two groups according to the stage of liver fibrosis assessed using MRI: no or mild fibrosis (F0-F1) and significant fibrosis (F2-F4). Framingham risk scores were calculated to evaluate cardiovascular risk factors, and patients underwent multiparametric cardiac and abdominal MRIs. (3) Results: The sample comprised 44 patients (28 with no or mild liver fibrosis and 16 with significant liver fibrosis). The mean age was 57.9 ± 12 years, and 41% were men. Most patients had high cardiac risk factors and carotid disease. Relative to patients with no or mild liver fibrosis, those with significant fibrosis had a higher median calcium score (p = 0.05) and increased myocardial extracellular volume (ECV; p = 0.02). Liver fibrosis correlated with cardiac fibrosis, represented by the ECV (r = 0.49, p < 0.001). The myocardial ECV differentiated patients with and without significant liver fibrosis (AUC = 0.78). (4) Conclusion: This study showed that diffuse myocardial fibrosis is associated with liver fibrosis in patients with NAFLD.

Exploring the Historical Background and Clinical Implications of Electrocardiogram in the Context of Chagas Disease Research.

Chagas disease (CD) remains one of the most significant endemic diseases in Latin America. Approximately 30% of individuals with CD develop the cardiac form, the main determinant of morbidity and mortality, which is characterized by typical electrocardiogram (ECG) changes caused by chronic chagasic cardiopathy (CCC). This review accentuates to how crucial it is for research teams and reference centers that treat patients with CD to standardize ECG in CCC. This was a non-systematic review of the literature. ECG is the most widely used examination in the diagnosis and evaluation of CCC, and it is also employed in epidemiological surveys, risk stratification for cardiovascular events and death, and monitoring the clinical progression of the disease. Carlos Chagas and Eurico Villela published the first work addressing CCC in 1922. Other works followed, including the study by Evandro Chagas' which was the first to perform ECG in CD, culminating in Francisco Laranja's seminal work in 1956. Since the 1980s, standardizations and ECG reading codes for CD have been established. This standardization aimed to code complex arrhythmias and characteristic ventricular conduction disorders and standardize ECG readings for clinical and epidemiological studies in CD. Nearly all existing electrocardiographic abnormalities can be found in CD, with a predominance of abnormalities in the formation and conduction of cardiac stimuli. The complex and heterogeneous substrate of CD with varied electrocardiographic manifestations poses a significant challenge when comparing studies involving patients with CCC, emphasizing the need for ECG standardization in CD.

Imaging Features and Complications of Facial Cosmetic Procedures.

Facial aesthetic procedures have become increasingly popular and complex, making knowledge of facial anatomy crucial for achieving desired outcomes without complications. Some of the most common procedures include blepharoplasty, bichectomy, face-lifts, facial implants, thread lifting, and fillers. Blepharoplasty and bichectomy are surgical procedures that respectively aim to restore youthful contours to the periorbita and create a slimmer lower face by removing Bichat fat from the maxillofacial region. Facial implants are used for aesthetic augmentation of the skeletal structure and restoration of facial contour by using biomaterials or autogenous bone grafts. Face-lift surgeries involve incisions and removal of excess skin, and thread lifts involve less invasive procedures performed by inserting threads beneath the skin, with the aim to lift the skin and thus reduce wrinkles and sagging. Fillers improve wrinkles and loss of facial volume, with biologic types made from animal, human, or bacterial sources (such as hyaluronic acid), while synthetic fillers include substances such as paraffin, silicone, calcium hydroxyapatite, polymethylmethacrylate microspheres, polyacrylamide hydrogel, hydroxyethyl-ethyl methacrylate, and poly-l-lactic acid. Synthetic fillers can be classified as rapidly resorbable (<12 months), slowly resorbable (<24 months), or permanent. Imaging modalities such as US, CT, and MRI can help identify and analyze each type of facial aesthetic procedure or filler, as well as their possible complications such as foreign-body granuloma, noninflammatory nodule, late intermittent persistent edema, filler migration, infection, or complications after removal of the buccal fat pad. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center The online slide presentation from the RSNA Annual Meeting is available for this article.

Pulse Wave Velocity of 8.2 m/s as a Threshold Associated with Cardiovascular Target Organ Damage Presence. / Velocidade de Onda de Pulso de 8,2m/s como Limiar Associado à Presença de Lesão de Órgão Alvo Cardiovascular.

BACKGROUND: Previous studies have established normal and reference values for Pulse Wave Velocity (PWV). However, the PWV value that has the strongest association with cardiovascular biomarkers remains poorly understood. OBJECTIVE: This study aimed to determine the PWV value more likely to be associated with left ventricular hypertrophy (LVH), increased intima-media thickness (IMT), and presence of carotid plaques in patients with hypertension. METHODS: This cross-sectional study included 119 patients. Analysis of receiver operating characteristic (ROC) curves was performed for each cardiovascular biomarker. Statistical significance was set at p < 0.05. RESULTS: According to the ROC curve analysis, the PWV values were 8.1 m/s, 8.2 m/s, and 8.7 for the LVH, IMT, and presence of carotid plaques, respectively. A PWV value of 8.2 m/s was identified as the best parameter to determine the three TOD biomarkers. PWV above 8.2 m/s was associated with increased CIMT (p = 0.004) and the presence of carotid plaques (p = 0.003) and LVH (p<0.001). PWV above 8.2 showed greater sensitivity for increased CIMT (AUC = 0.678, sensitivity = 62.2), LVH (AUC = 0.717, sensitivity = 87.2), and the presence of plaques (AUC = 0.649, sensitivity = 74.51) in the ROC curve analysis. CONCLUSION: The PWV value 8.2 m/s was more sensitive in early identifying the existence of cardiovascular biomarkers of TOD.

FUNDAMENTO: Estudos prévios estabeleceram valores de normalidade e de referência da Velocidade de Onda de Pulso (VOP). Porém, qual valor de VOP que apresenta a associação mais forte com biomarcadores cardiovasculares ainda é pouco conhecido. OBJETIVO: Identificar o valor de VOP com maior possibilidade de estar associado com hipertrofia ventricular esquerda (HVE), aumento da espessura íntima-média carotídea (EIMC), e presença de placas carotídeas em pacientes hipertensos. MÉTODOS: Este é um estudo transversal de 119 pacientes. Análise de curvas características de operação do receptor (ROC) foi realizada para cada biomarcador cardiovascular. A diferença estatística foi estabelecida em p<0,05. RESULTADOS: Segundo análises das curvas ROC, valores de VOP de 8,1m/s para HVE, 8,2m/s para EMIC aumentada e 8,7m/s para a presença de placa carotídea foram encontrados, respectivamente. O valor de VOP de 8,2m/s foi definido como melhor o parâmetro para encontrar os três biomarcadores de LOA. A VOP acima de 8,2m/s associou-se ao aumento da EMIC (p = 0,004), à presença de placas carotídeas (p = 0,003) e à HVE (p < 0,001). A VOP acima de 8,2m/s apresentou maior sensibilidade para EMIC aumentada (AUC = 0,678, sensibilidade 62,2), HVE (AUC = 0,717, sensibilidade 87,2), e presença de placas (AUC = 0,649, sensibilidade 74,51) na análise das curvas ROC. CONCLUSÃO: O valor de 8,2m/s de VOP foi mais sensível em identificar, precocemente, a existência de biomarcadores cardiovasculares de LOA.

Corrigendum: Home-based exercise program in the indeterminate form of Chagas disease (PEDI-CHAGAS study): a study protocol for a randomized clinical trial.

[This corrects the article DOI: 10.3389/fmed.2022.1087188.].

Use of PET/CT to detect myocardial inflammation and the risk of malignant arrhythmia in chronic Chagas disease.

BACKGROUND: Chagas heart disease (CHD) is characterized by progressive myocardial inflammation associated with myocardial fibrosis and segmental abnormalities that may lead to malignant ventricular arrhythmia and sudden cardiac death. This arrhythmia might be related to the persistence of parasitemia or inflammation in the myocardium in late-stage CHD. Positron emission tomography/computed tomography (PET/CT) has been used to detect myocardial inflammation in non-ischemic cardiomyopathies, such as sarcoidosis, and might be useful for risk prediction in patients with CHD. METHODS AND RESULTS: Twenty-four outpatients with chronic CHD were enrolled in this prospective cross-sectional study between May 2019 and March 2022. The patients were divided into two groups: those with sustained ventricular tachycardia and/or aborted sudden cardiac death who required implantable cardioverter-defibrillators, and those with the same stages of CHD and no complex ventricular arrhythmia. Patients underwent 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATOC PET/CT, and blood samples were collected for qualitative parasite assessment by polymerase chain reaction. Although similar proportions of patients with and without complex ventricular arrhythmia showed 18F-FDG and 68Ga-DOTATOC uptake, 68Ga-DOTATOC corrected SUVmax was higher in patients with complex arrhythmia (3.4 vs 1.7; P = .046), suggesting that inflammation could be associated with the presence of malignant arrhythmia in the late stages of CHD. We also detected Trypanosoma cruzi in both groups, with a nonsignificant trend of increased parasitemia in the group with malignant arrhythmia (66.7% vs 33.3%). CONCLUSION: 18F-FDG and 68Ga-DOTATOC uptake on PET/CT may be useful for the detection of myocardial inflammation in patients with Chagas cardiomyopathy, and 68Ga-DOTATOC uptake may be associated with the presence of malignant arrhythmia, with potential therapeutic implications.

Biomarkers and Echocardiographic Predictors of Cardiovascular Outcome in Patients With Chronic Chagas Disease.

Background Chagas disease (CD) presents an ominous prognosis. The predictive value of biomarkers and new echocardiogram parameters in adjusted models have not been well studied. Methods and Results There were 361 patients with chronic CD (57.6% men, 61±11 years of age, clinical forms: indeterminate 27.1%, cardiac 56.6%, digestive 3.6%, cardiodigestive 12.7%) included in this single-center, observational, prospective longitudinal study. Echocardiographic evaluation included strain analyses of left atrial, left ventricular (LV), and right ventricular and 3-dimensional analyses of left atrial and LV volumes. Biomarkers included cardiac troponin I, brain natriuretic peptide, transforming growth factor ß1, tumor necrosis factor, matrix metalloproteinases, and Trypanosoma cruzi polymerase chain reaction. The studied end point was a composite of CD-related mortality, heart transplant, hospital admission due to worsening heart failure, or new cardiac device insertion. Event-free survival was analyzed by multivariable regression analyses adjusted for competing risks. P values <0.05 were considered significant. The composite event occurred in 79 patients after 4.9±2.0 years follow-up. LV end-diastolic volume (hazard ratio [HR], 1.01 [95% CI, 1.00-1.02]; P=0.02), peak negative global atrial strain (HR, 1.08 [95% CI, 1.00-1.17]; P=0.04), LV global circumferential strain (HR, 1.12 [95% CI, 1.04-1.21]; P=0.003), LV torsion (HR, 0.55 [95% CI, 0.35-0.81]; P=0.003), brain natriuretic peptide (HR, 2.03 [95% CI, 1.23-3.34]; P=0.005), and positive T cruzi polymerase chain reaction (HR, 1.80 [95% CI, 1.12-2.91]; P=0.01) were end point predictors independent from age, sex, 2-dimensional echocardiographic indexes, hypertension, previous cardiac device, and CD cardiac form. Conclusions Two-dimensional strain- and 3-dimensional-derived parameters, brain natriuretic peptide, and positive T cruzi polymerase chain reaction can be useful for prediction of CD cardiovascular events.