Predictors of Trypanosoma cruzi PCR positivity in patients with chronic Chagas disease.

BACKGROUND: A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD). OBJECTIVES: To study the association of clinical, electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD. METHODS: This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant. FINDINGS: Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 [95% confidence interval (CI) 0.30-0.93]; p = 0.03}, right bundle branch block [OR 1.78 (95% CI 1.09-2.89); p = 0.02], and history of trypanocidal treatment [OR 0.13 (95% CI 0.04-0.38); p = 0.0002]. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR. MAIN CONCLUSIONS: Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.

Correlation of transforming growth factor-ß1 and tumour necrosis factor levels with left ventricular function in Chagas disease.

BACKGROUND: Transforming growth factor ß1 (TGF-ß1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. OBJECTIVES: We determined whether TGF-ß1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. METHODS: This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-ß1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. FINDINGS: TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-ß1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. CONCLUSIONS: TNF is increased, while TGF-ß1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-ß1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients.

Socio-epidemiological factors and comorbidities associated with Chagas disease manifestations in two urban reference health care centres in Rio de Janeiro, Brazil.

BACKGROUND: Chagas disease (CD) is still an important public health issue in Latin America. This study aims to analyse the association between socio-epidemiological factors and comorbidities with clinical manifestations of CD. METHODS: We performed a cross-sectional study of 985 adult patients (65±11 y; 59.5% women) with CD. Data collection was based on questionnaires and medical records review. CD clinical forms (indeterminate, digestive, cardiac and cardiodigestive) and the stages of the cardiac form were classified according to the II Brazilian Consensus on CD. Statistical analyses were based on univariate and multivariate logistic regression. RESULTS: Older age and Brazilian birth state (Minas Gerais and Bahia) were associated with a greater likelihood of the cardiac form of CD. A greater likelihood of the digestive form was seen in men and those of older age. Patients with arterial hypertension and diabetes were less likely to have the digestive form. Men had a greater likelihood of having a more severe cardiac presentation. Those from Minas Gerais and Bahia states had a greater likelihood of having stage B1 or B2. CONCLUSIONS: The results reinforce the aging of the CD population living in urban areas in Brazil, the high prevalence of comorbidities and that epidemiology, sex and the presence of comorbidities may be related to the clinical form of CD.

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.].

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.

Two-dimensional strain derived parameters provide independent predictors of progression to Chagas cardiomyopathy and mortality in patients with Chagas disease.

BACKGROUND: Patients with chronic Chagas disease (CD) cardiomyopathy have a high mortality. We evaluated if two-dimensional (2D) strain (ε) parameters provide independent predictors of progression to CD cardiomyopathy and all-cause mortality. METHODS: A total of 408 patients with chronic CD (58.6% women; 53 ± 11 years; clinical forms: indeterminate 34.1%, cardiac 57.6%, digestive 1.2%, cardiodigestive 7.1%) were consecutively included in this single-center prospective longitudinal study. Echocardiographic evaluation included left atrial and left ventricular (LV) function on ε analyses. Primary end-point was a composite of all-cause mortality or heart transplant. Secondary end-point was CD progression defined as the occurrence of changes typical of CD in electrocardiogram, sustained ventricular tachycardia, wall motion abnormalities, or heart failure among patients with the indeterminate form at baseline. Multivariable Cox-proportional-hazards regression analyses were performed to test if 2D ε parameters were associated with the studied end-points. P values < 0.05 were considered significant. RESULTS: The primary end-point occurred in 91 patients after a follow-up of 6.5 ± 2.7 years. CD progression occurred in 26 out of 144 patients without cardiac form at baseline (2.88 cases/100 patient-years). Peak LV circumferential (HR 1.09, 95% CI 1.01-1.18, P = .02) and radial (HR 0.97, 95% CI 0.95-0.99, P = .007) ε, and LV torsion (HR 0.51, 95% CI 0.35-0.74, P = .0004) were independent predictors of the primary end-point. Peak LV radial ε (HR 0.96, 95% CI 0.93-0.99, P = .03) was an independent predictor of CD progression. CONCLUSIONS: Therefore, 2D ε derived parameters can be useful for CD progression and mortality prediction.

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

Background: Chagas disease (CD) is a neglected endemic disease with worldwide impact due to migration. Approximately 50-70% of individuals in the chronic phase of CD present the indeterminate form, characterized by parasitological and/or serological evidence of Trypanosoma cruzi infection, but without clinical signs and symptoms. Subclinical abnormalities have been reported in indeterminate form of CD, including pro-inflammatory states and alterations in cardiac function, biomarkers and autonomic modulation. Moreover, individuals with CD are usually impacted on their personal and professional life, making social insertion difficult and impacting their mental health and quality of life (QoL). Physical exercise has been acknowledged as an important strategy to prevent and control numerous chronic-degenerative diseases, but unexplored in individuals with the indeterminate form of CD. The PEDI-CHAGAS study (which stands for "Home-Based Exercise Program in the Indeterminate Form of Chagas Disease" in Portuguese) aims to evaluate the effects of a home-based exercise program on physical and mental health outcomes in individuals with indeterminate form of CD. Methods and design: The PEDI-CHAGAS is a two-arm (exercise and control) phase 3 superiority randomized clinical trial including patients with indeterminate form of CD. The exclusion criteria are <18 years old, evidence of non-Chagasic cardiomyopathy, musculoskeletal or cognitive limitations that preclude the realization of exercise protocol, clinical contraindication for regular exercise, and regular physical exercise (≥1 × per week). Participants will be assessed at baseline, and after three and 6 months of follow-up. The primary outcome will be QoL. Secondary outcomes will include blood pressure, physical fitness components, nutritional status, fatigability, autonomic modulation, cardiac morphology and function, low back pain, depression and anxiety, stress, sleep quality, medication use and adherence, and biochemical, inflammatory and cardiac biomarkers. Participants in the intervention group will undergo a home-based exercise program whilst those in the control group will receive only general information regarding the benefits of physical activity. Both groups will receive the same general nutritional counseling consisting of general orientations about healthy diets. Conclusion: The findings from the present study may support public health intervention strategies to improve physical and mental health parameters to be implemented more effectively in this population. Clinical trial registration: [https://ensaiosclinicos.gov.br/rg/RBR-10yxgcr9/], identifier [U1111-1263-0153].

Chagas heart disease: An overview of diagnosis, manifestations, treatment, and care.

Chagas heart disease (CHD) affects approximately 30% of patients chronically infected with the protozoa Trypanosoma cruzi. CHD is classified into four stages of increasing severity according to electrocardiographic, echocardiographic, and clinical criteria. CHD presents with a myriad of clinical manifestations, but its main complications are sudden cardiac death, heart failure, and stroke. Importantly, CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies, and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies. Among patients with CHD, approximately 90% of deaths can be attributed to complications of Chagas disease. Sudden cardiac death is the most common cause of death (55%-60%), followed by heart failure (25%-30%) and stroke (10%-15%). The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with. Therefore, the management of CHD is challenging, and in this review, we present the most updated available data to help clinicians and cardiologists in the care of these patients. We describe the clinical manifestations, diagnosis and classification criteria, risk stratification, and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.

Effects of Selenium treatment on cardiac function in Chagas heart disease: Results from the STCC randomized Trial.

BACKGROUND: Chagas disease (caused by Trypanosoma cruzi infection) evolves to chronic chagasic cardiomyopathy (CCC) affecting 1.8 million people worldwide. This is the first randomized, placebo-controlled, double-blinded, clinical trial designed to estimate efficacy and safety of selenium (Se) treatment in CCC. METHODS: 66 patients with CCC stages B1 (left ventricular ejection fraction [LVEF] > 45% and no heart failure; n = 54) or B2 (LVEF < 45% and no heart failure; n = 12) were randomly assigned to receive 100 mcg/day sodium selenite (Se, n = 32) or placebo (Pla, n = 34) for one year (study period: May 2014-September 2018). LVEF changes over time and adverse effects were investigated. Trial registration number: NCT00875173 (clinicaltrials.gov). FINDINGS: No significant differences between the two groups were observed for the primary outcome: mean LVEF after 6 (ß= +1.1 p = 0.51 for Se vs Pla) and 12 months (ß= +2.1; p = 0.23). In a subgroup analysis, statistically significant longitudinal changes were observed for mean LVEF in the stage B2 subgroup (ß= +10.1; p = 0.02 for Se [n = 4] vs Pla [n = 8]). Se treatment was safe for CCC patients, and the few adverse effects observed were similarly distributed across the two groups. INTERPRETATION: Se treatment did not improve cardiac function (evaluated from LVEF) in CCC. However, in the subgroup of patients at B2 stage, a potential beneficial influence of Se was observed. Complementary studies are necessary to explore diverse Se dose and/or associations in different CCC stages (B2 and C), as well as in A and B1 stages with longer follow-up. FUNDING: Brazilian Ministry of Health, Fiocruz, CNPq, FAPERJ.

Left Atrial Structure and Function Predictors of New-Onset Atrial Fibrillation in Patients with Chagas Disease.

BACKGROUND: Atrial fibrillation (AF) carries ominous consequences in patients with Chagas disease. The aim of this study was to determine whether left atrial (LA) volume and function assessed using three-dimensional echocardiographic (3DE) imaging and two-dimensional speckle-tracking echocardiographic deformation analysis of strain (ε) could predict new-onset AF in patients with Chagas disease. METHODS: A total of 392 adult patients with chronic Chagas disease (59% women; mean age, 53 ± 11 years) who underwent echocardiography were consecutively enrolled in this prospective longitudinal study. Echocardiographic evaluation included two-dimensional (2D) Doppler echocardiography, with evaluation of left ventricular systolic and diastolic function, LA size, and LA and left ventricular function on 3DE and ε analyses. Multivariate Cox proportional-hazards regression analysis models adjusting for age, sex, hypertension, presence of a pacemaker, and 2D Doppler echocardiographic parameters were used to test if the variables of interest had independent prognostic value for AF prediction. RESULTS: Patients with Chagas disease were followed for 5.6 ± 2.7 years. Among these, 139 (35.5%) had the indeterminate form, 224 (57.1%) had the cardiac form, five (1.3%) had the digestive form, and 24 (6.1%) had the cardiodigestive form. The study end point of AF occurred in 45 patients. Total LA emptying fraction (hazard ratio, 0.93; 95% CI, 0.89-0.98; P = .002), passive LA emptying fraction (HR, 0.95; 95% CI, 0.91-0.99; P = .02), and peak negative global LA ε (HR, 1.22; 95% CI, 1.05-1.41; P = .01) were predictors of new-onset AF independent of clinical and 2D Doppler echocardiographic parameters. CONCLUSIONS: LA function assessed on 3DE and ε analyses predicts new-onset AF in patients with Chagas disease independent of clinical and 2D Doppler echocardiographic indexes.

Predictors of Trypanosoma cruzi PCR positivity in patients with chronic Chagas disease

BACKGROUND A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD). OBJECTIVES To study the association of clinical, electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD. METHODS This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant. FINDINGS Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 [95% confidence interval (CI) 0.30-0.93]; p = 0.03}, right bundle branch block [OR 1.78 (95% CI 1.09-2.89); p = 0.02], and history of trypanocidal treatment [OR 0.13 (95% CI 0.04-0.38); p = 0.0002]. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR. MAIN CONCLUSIONS Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.

Analysis of Regional Left Ventricular Strain in Patients with Chagas Disease and Normal Left Ventricular Systolic Function.

BACKGROUND: Chagas heart disease has a high socioeconomic burden, and any strategy to detect early myocardial damage is welcome. Speckle-tracking echocardiography assesses global and segmental left ventricular (LV) systolic function, yielding values of two-dimensional strain (ε). The aim of this study was to determine if patients with chronic Chagas disease and normal LV ejection fractions present abnormalities in global and segmental LV ε. METHODS: In this prospective study, patients with Chagas disease with no evidence of cardiac involvement (group I; n = 83) or at stage A of the cardiac form (i.e., with changes limited to the electrocardiogram) (group A; n = 42) and 43 control subjects (group C) underwent evaluation of global and segmental LV ε by speckle-tracking echocardiography. A subset of randomly selected patients in group A underwent cardiac magnetic resonance imaging and repeated echocardiography 3.5 ± 0.8 years after the first evaluation. RESULTS: Mean age, chamber dimensions, and LV ejection fraction were similar among the groups. Global longitudinal (group C, -19 ± 2%; group I, -19 ± 2%; group A, -19 ± 2%), circumferential (group C, -19 ± 3%; group I, -20 ± 3%; group A, -19 ± 3%), and radial (group C, 46 ± 10%; group I, 45 ± 13%; group A, 42 ± 14%) LV ε were similar among the groups. Segmental longitudinal, circumferential, and radial LV ε were similar across the studied groups. Seven of 14 patients had areas of fibrosis on cardiac magnetic resonance imaging. Patients with fibrosis had lower global longitudinal (-15 ± 2% vs -18 ± 2%, P = .004), circumferential (-14 ± 2% vs -19 ± 2%, P = .002), and radial LV ε (36 ± 13% vs 54 ± 12%, P = .02) than those without cardiac fibrosis despite similar LV ejection fractions. Patients with fibrosis had lower radial LV ε in the basal inferoseptal wall than patients without cardiac fibrosis (27 ± 17% vs 60 ± 15%, P = .04). CONCLUSIONS: Patients with chronic Chagas disease and normal global and segmental LV systolic function on two-dimensional echocardiography had global and segmental LV ε similar to that of control subjects. However, those in the early stages of the cardiac form and cardiac fibrosis had lower global longitudinal, circumferential, and radial LV ε.

Correlation of transforming growth factor-b and tumour necrosis factor levels with left ventricular function in Chagas disease

BACKGROUND Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. OBJECTIVES We determined whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. METHODS This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. FINDINGS TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. CONCLUSIONS TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients.

Impact of pharmaceutical care on the quality of life of patients with Chagas disease and heart failure: randomized clinical trial.

BACKGROUND: Pharmaceutical care is the direct interaction between pharmacist and patient, in order to improve therapeutic compliance, promote adequate pharmacotherapeutic follow-up, and improve quality of life. Pharmaceutical care may be effective in reducing complications and in improving the quality of life of patients with chronic diseases, like Chagas heart disease, while bringing a positive impact on health system costs. The morbidity and mortality indexes for patients with Chagas heart disease are high, especially if this heart disease is complicated by heart failure. In this setting, we hypothesize that pharmaceutical care might be an important tool for the clinical management of these patients by improving their quality of life, as a better compliance to their treatment and the avoidance and prompt correction of drug-related problems will minimize their symptoms, improve their functional class, and decrease the number of hospital admissions. Therefore, the aim of this trial is to evaluate the contribution of pharmaceutical care to clinical treatment of patients with Chagas heart disease complicated by heart failure. METHODS/DESIGN: A prospective, single-center randomized clinical trial will be conducted in patients with Chagas heart disease complicated by heart failure. A total of 88 patients will be randomly assigned into two parallel groups: an intervention group will receive standard care and pharmaceutical care, and a control group will receive only standard care. Both groups will be subjected to a follow-up period of 12 months. The primary outcome of this trial is the evaluation of quality of life, measured by the 36-item short-form and the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include drug-related problems, exercise tolerance as measured by the standard six-minute-walk test, and compliance. DISCUSSION: Patients with Chagas heart disease complicated by heart failure under pharmaceutical care are expected to improve their quality of life, present with a lower incidence of drug-related problems, improve their functional capacity, and improve in their compliance to treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01566617.