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BACKGROUND Chagas disease is one of the most common diseases in Latin-America, and cardiac involvement is a significant cause of death. Assessment of myocardial strain may detect early myocardial damage. OBJECTIVES To determine differences in longitudinal strain using speckle tracking to assess regional and global left ventricular function in patients with the indeterminate form of Chagas disease, in comparison with a control group. METHODS This is a retrospective matched case-control study, conducted in a single center. We evaluated 45 adult patients with Chagas disease, diagnosed with 2 serological methods, without evidence of cardiac involvement, who were compared with 45 healthy control subjects, who were sex- and age-matched. All patients underwent Doppler echocardiography and longitudinal strain with speckle tracking. RESULTS Median age was 59 years, and 60% were female. Echocardiographic parameters were similar in patients with Chagas and control subjects. In patients with Chagas, global strain differed significantly from that of control subjects (-17 vs -20.3, P < .001). Segmental strain showed 7 abnormal segments in patients with Chagas (P < .05). CONCLUSIONS In patients with the indeterminate form of Chagas disease, global and segmental longitudinal peak systolic strain is reduced compared with healthy subjects, thus suggesting that it could be a sensitive technique to detect early myocardial damage. These findings could provide useful information regarding the pathophysiology of cardiac involvement and understand whether they might have prognostic usefulness or help develop strategies to modify the course and prognosis of patients with Chagas disease. A longitudinal prospective study would be necessary to validate our findings.

Malaltia de Chagas; Trypanosoma cruzi; Variabilitat genètica Chagas disease; Trypanosoma cruzi; Genetic variability Enfermedad de Chagas; Trypanosoma cruzi; Variabilidad genética Background: Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain. Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis. Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD. Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD. This work was supported by São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2018/22093-4), São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2019/11943-0), São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2016/25403-9), and Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, PROSICS Barcelona, Spain.

Objective Investigate whether heart rate variability (HRV) indices can be used to predict morpho-functional parameters obtained from the echocardiogram in a population of patients with Chagas disease (CD). Methods Sixty-three patients with CD and a recent echocardiogram had their ECG and respiratory signals recorded for 15 min. The cardiac interval series were generated from the ECG and 27 HRV indices, plus the respiratory frequency, were calculated. The correlation between HRV and echocardiographic variables was estimated. The HRV indices were also utilized as inputs in four machine learning schemes to create predictive models for numeric and categorical echocardiographic parameters. Attribute selection schemes were also performed to identify the subset of HRV indices that best represent each parameter for each machine learning algorithm. Results Only three echocardiographic parameters had no HRV index significantly correlated to them. The most frequently selected HRV index in the attribute selection process was the fractal short-term scaling exponent. The regression models (numeric parameters) reached reasonable performance (R > 0.5) for all except two parameters, while the classification models (categorical variables) achieved better performance, with precision and recall values higher than 0.74. Conclusion HRV indices, both isolated and combined, are associated with cardiac morpho-functional properties in patients with CD, and may be used to predict echocardiographic parameters. Significance The possibility of modeling the cardiac morpho-functional parameters in patients with CD using HRV indices opens the possibility to use HRV for risk assessment in patients with CD, especially those harboring the indeterminate form of the disease.

Chagas disease (CD) remains a serious endemic disease in Latin America and a major public health problem. Because of globalization, the disease has spread to non-endemic areas in the northern hemisphere. In the chronic phase of the disease, most patients present with the indeterminate form (IF), characterized by positive serology for Trypanosoma cruzi, absence of clinical findings, and normal findings in electrocardiogram (ECG). IF was not recognized as a clinical entity until decades after the discovery of the disease, and only in the 1940-50s, it was categorized as a form of CD, and its conceptual definition was ratified in the 1980s. Children, adolescents, and young adults with the IF benefit from etiological treatment and tend to have less progression to heart disease in the long term than the untreated ones. IF patients have an essentially benign clinical condition, and their prognosis can be compared to that of healthy individuals with normal ECG findings. Currently, because of aging, patients with the IF have comorbidities that require attention in health services.

Background Chagas disease (CD) remains an important endemic disease in Latin America. However, CD became globalized in recent decades. The majority of the chronically infected individuals did not receive etiologic treatment for several reasons, among them the most conspicuous is the lack of access to diagnosis. The impact of trypanocidal treatment on CD chronic phase, without cardiac involvement (indeterminate form ICF), is yet to be determined. We aimed to evaluate the effect of trypanocidal treatment with benznidazole (BZN) on the rate of progression to Chagas heart disease in patients with ICF. Methods This is a retrospective cohort observational study including patients with ICF treated with BZN and compared to a group of non-treated patients matched for age, sex, region of origin, and the year of cohort entry. We reviewed the medical charts of all patients followed from May 1987 to June 2020 at the outpatient center of the Evandro Chagas National Institute of Infectious Diseases (INI) of the Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. Patients' follow-up included at least one annual medical visit and one annual electrocardiogram (ECG). Echocardiographic exams were performed at baseline and during the follow-up. Disease progression from ICF to cardiac form was defined by changes in baseline ECG. Cumulative incidence and the incidence rate were described in the incidence analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association between BZN and CD progression, cardiovascular events or death. Findings One hundred and fourteen treated patients met the study inclusion criteria. A comparison group of 114 non-treated patients matched for age, sex, region of origin, and the year of cohort entry was also included, totalizing 228 patients. Most patients included in the study were male (70.2%), and their mean age was 31.3 (+7.4) years. Over a median follow-up of 15.1 years (ranging from 1.0 to 32.4), the cumulative CD progression incidence in treated patients was 7.9% vs. 21.1% in the non-treated group (p = 0.04) and the CD progression rate was 0.49 per 1.000 patients/year in treated patients vs. 1.10 per 1.000 patients/year for non-treated patients (p = 0.02). BZN treatment was associated with a decreased risk of CD progression in both unadjusted (HR 0.46; 95%CI 0.21 to 0.98) and adjusted (HR 0.43; 95%CI 0.19 to 0.96) models and with a decreased risk of occurrence of the composite of cardiovascular events only in the adjusted (HR 0.15; 95%CI 0.03 to 0.80) model. No association was observed between BZN treatment and mortality. Interpretation In a long-term follow-up, BZN treatment was associated with a decreased incidence of CD progression from ICF to the cardiac form and also with a decreased risk of cardiovascular events. Therefore, our results indicate that BZN treatment for CD patients with ICF should be implemented into clinical practice.

Chagas disease (CD) will account for 200,000 cardiovascular deaths worldwide over the next 5 years. Early detection of chronic Chagas cardiomyopathy (CCC) is a challenge. We aimed to test if speckle-tracking echocardiography (STE) can detect incipient myocardial damage in CD. METHODS: Among 325 individuals with positive serological tests, 25 (age 55±12yrs) were selected to compose the group with indeterminate form of Chagas disease (IFCD), based on stringent criteria of being asymptomatic and with normal EKG/X-ray studies. This group was compared with a group of 20 patients with CCC (55±11yrs) and a group of 20 non-infected matched control (NC) subjects (48±10yrs). CD patients and NC were submitted to STE and CD patients were submitted to cardiac magnetic resonance (CMR) with late gadolinium administration to detect cardiac fibrosis by the late enhancement technique. Global longitudinal strain (GLS), circumferential (GCS) and radial strain (GRS) were defined as the average of segments measured from three apical view (GLS) and short axis views (GRS and GCS). Regional left ventricular (LV) longitudinal strain (Reg LS) was measured from each of the 17 segments. Twist was measured as systolic peak difference between basal and apical rotation and indexed to LV length to express torsion. RESULTS: STE global indices (GLS, GCS, twist and torsion) were reduced in CCC vs NC (GLS: -14±6.3% vs -19.3±1.6%, p = 0.001; GCS: -13.6±5.2% vs -17.3 ±2.8%; p = 0.008; twist: 8±7° vs 14±7°, p = 0.01 and torsion: 0.96±1°/cm vs 1.9±1°/cm, p = 0.005), but showed no differences in IFCD vs NC. RegLS was reduced in IFCD vs NC in four LV segments: basal-inferior (-16.3±3.3% vs -18.6±2.2%, p = 0.013), basal inferoseptal (-13.1±3.4 vs -15.2±2.7, p = 0.019), mid-inferoseptal (-17.7±3.2 vs -19.4±2, p = 0.032) and mid-inferolateral (-15.2±3.5 vs -17.8±2.8, p = 0.014). These abnormalities in RegLS occurred in the absence of myocardial fibrosis detectable with CMR in nearly 92% of subjects with IFCD, while myocardial fibrosis was present in 65% with CCC. CONCLUSION: RegLS detects early regional impairment of myocardial strain that is independent from fibrosis in IFCD subjects., Author summary Regional longitudinal strain is reduced in IFCD before significant fibrosis. As CD progresses to CF, global STE measurements of left ventricle (GLS, GCS, twist and torsion) and GLS of right ventricle are reduced. Early abnormal strain pattern of CD comprises inferior, septoinferior and inferolateral segments of LV. Recognizing the regional strain pattern of Chagas cardiomyopathy may help identifying the disease even at early stages.

Key Points Question What is the risk of developing cardiomyopathy among patients with the acute phase of Chagas infection or the indeterminate chronic form of Chagas disease? Findings In this systematic review and meta-analysis of 32 studies of patients with Chagas disease, the pooled estimated annual rate of cardiomyopathy was 4.6% among patients with acute Chagas infection and 1.9% among patients with indeterminate chronic Chagas disease. Meaning The findings indicate that asymptomatic individuals with indeterminate chronic Chagas disease without cardiac injury and individuals with acute Chagas infection may have a significant risk of developing chronic cardiomyopathy., Importance Chagas cardiomyopathy is associated with substantial morbidity and mortality. Precise estimates of the risk of developing cardiomyopathy among patients with the acute or indeterminate chronic forms of Chagas disease are lacking. Objective To estimate the risk of developing chronic cardiomyopathy in patients with acute and indeterminate chronic forms of Chagas disease. Data Sources A systematic search in the Cochrane Library, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), Medline, and Web of Science Core Collection databases was conducted from October 8 to October 24, 2018. Studies published between January 1, 1946, and October 24, 2018, that were written in the English, Spanish, and Portuguese languages were included. Search terms included Chagas disease; development of cardiomyopathy; latency duration; and determinants of the Chagas latency period. Study Selection Longitudinal observational studies of participants diagnosed with the acute phase of Chagas infection or the indeterminate chronic form of Chagas disease who were followed up until the development of cardiomyopathy were included. Studies were excluded if they did not provide sufficient outcome data. Of 10 761 records initially screened, 32 studies met the criteria for analysis. Data Extraction and Synthesis Critical appraisals of studies were performed using checklists from the Joanna Briggs Institute Reviewer’s Manual, and data were collected from published studies. A random-effects meta-analysis was used to obtain pooled estimated annual rates. Data were analyzed from September 11 to December 4, 2019. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for the registration of the protocol, data collection and integrity, assessment of bias, and sensitivity analyses. Main Outcomes and Measures Main outcomes were defined as the composite of the development of any new arrhythmias or changes in electrocardiogram results, dilated cardiomyopathy and segmental wall motion abnormalities in echocardiogram results, and mortality associated with Chagas disease. Results A total of 5005 records were screened for eligibility. Of those, 298 full-text articles were reviewed, and 178 of those articles were considered for inclusion in the quantitative synthesis. After exclusions, 32 studies that included longitudinal observational outcomes were selected for the analysis; 23 of those studies comprised patients with the indeterminate chronic form of Chagas disease, and 9 of those studies comprised patients in the acute phase of Chagas infection. The analysis indicated that the pooled estimated annual rate of cardiomyopathy development was 1.9% (95% CI, 1.3%-3.0%; I2 = 98.0%; τ2 [ln scale] = 0.9992) in patients with indeterminate chronic Chagas disease and 4.6% (95% CI, 2.7%-7.9%; I2 = 86.6%; τ2 [ln scale] = 0.4946) in patients with acute Chagas infection. Conclusions and Relevance Patients with the indeterminate chronic form of Chagas disease had a significant annual risk of developing cardiomyopathy. The annual risk was more than double among patients in the acute phase of Chagas infection., This systematic review and meta-analysis assesses the risk of developing chronic cardiomyopathy among patients with acute and indeterminate chronic forms of Chagas disease.

OBJECTIVES This study was designed to investigate digestive and heart associations, using esophageal transit scintigraphy in three different groups: patients exclusively with the dilated cardiac form of Chagas disease (DCCh), an indeterminate form of Chagas disease, and healthy controls. As a hypothesis, we assumed that autonomic chagasic denervation is a global process. MATERIALS AND METHODS Twenty healthy controls and 75 outpatients with Chagas disease, divided into indeterminate form (n = 33) and (DCCh, n = 42), underwent esophageal scitigraphy. The esophageal transit time (ETT) and percentage of esophageal emptying (%EE) were analyzed by group and correlated with left ventricular ejection fraction (LVEF). RESULTS ETT alterations were found in 57% of indeterminate form and 80% of DCCh. The observed values of ETT and %EE in Chagas disease groups were significantly different from the controls (P-value

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 (e) 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 e 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 e (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 e analyses predicts new-onset AF in patients with Chagas disease independent of clinical and 2D Doppler echocardiographic indexes.

Introduction According to the WHO, Chagas disease affects 8 to 10 million people, mainly in the Americas and in some European countries, with more than 10 thousand annual deaths. It presents an acute phase followed by a chronic, categorized as indeterminate, cardiac or digestive forms. After infestation, most patients remain asymptomatic, but 40% progress to symptomatic form at the rate of 1.8 to 5% patients/year. Evidence of myocardial fibrosis in 41% of these patients was found by magnetic resonance imaging. Objective To evaluate, by echocardiography, patients with Chagas disease, indeterminate phase, analysing dimensions, function and parameters of deformation and mechanical dispersion in left and right cardiac cavities. Method The study included 44 asymptomatic patients, 36 female, mean age 51 ± 10 years with positive Chagas serology and a control group of 44 healthy individuals, 35 female, mean age 52 ± 10 years. Left and right cavitary dimensions were evaluated, systolic and diastolic function, global myocardial deformation and mechanical dispersion. The groups were compared by the paired "t" test with significance level Results Demographic data (age, body surface area) with no significant differences. Left ventricular (LV) diameters (p Conclusion Asymptomatic patients with Chagas disease (undetermined phase), when compared with healthy individuals of the same age group, presented larger cavitary diameters, diastolic disfunction and, deformation parameters of the left and right ventricles, with increased mechanical dispersion in both chambers. These data seem to corroborate recent results obtained by magnetic resonance imaging with gadolinium, suggesting areas of myocardial fibrosis in these patients.

INTRODUCTION In order to detect Trypanosoma cruzi and determine the genetic profiles of the parasite during the chronic phase of Chagas disease (ChD), parasitological and molecular diagnostic methods were used to assess the blood of 91 patients without specific prior treatment. METHODS Blood samples were collected from 68 patients with cardiac ChD and 23 patients with an indeterminate form of ChD, followed by evaluation using blood culture and polymerase chain reaction. T . cruzi isolates were genotyped using three different genetic markers. RESULTS: Blood culture was positive in 54.9% of all patients, among which 60.3% had the cardiac form of ChD, and 39.1% the indeterminate form of ChD. There were no significant differences in blood culture positivity among patients with cardiac and indeterminate forms. Additionally, patient age and clinical forms did not influence blood culture results. Polymerase chain reaction (PCR) was positive in 98.9% of patients, although comparisons between blood culture and PCR results showed that the two techniques did not agree. Forty-two T . cruzi stocks were isolated, and TcII was detected in 95.2% of isolates. Additionally, one isolate corresponded to TcIII or TcIV, and another corresponded to TcV or TcVI. CONCLUSIONS Blood culture and PCR were both effective for identifying T. cruzi using a single blood sample, and their association did not improve parasite detection. However, we were not able to establish an association between the clinical form of ChD and the genetic profile of the parasite.

Chagas disease (CD) is highly endemic in Latin America, and has been emerging in developed countries. Early diagnosis of left ventricular (LV) systolic dysfunction, routinely done by echocardiography, is crucial for therapy. Speckle tracking echocardiography allows determination of LV segmental rotations, twist/torsion, and this analysis may disclose an unapparent myocardial contractile deficit in initial stages of CD. Therefore, this study aimed to highlight a possible unapparent myocardial contractile deficit in CD indeterminate form (IF) by a comprehensive torsional mechanics analysis. Patients with CDIF diagnosis, initial chagasic cardiomyopathy (CCMP characterized by ECG abnormalities and LVEF > 0.55), and normal controls were prospectively enrolled, and underwent conventional echocardiogram with images acquisition for STE offline analysis. Target parameters were basal and apical rotations, and calculation of twist and torsion. A total of 42 patients were included (CDIF, eight; CCMP, 13; and 21 controls). Chagasic patients had a mean age of 55 years, five (24 %) men, and controls, 50 years, seven (33 %) men. Torsional mechanics analyzes resulted in no significant difference in all parameters studied between groups. Twist in CDIF was 20.8° ± 6.5°; CCMP, 19.0° ± 3.5° and controls, 19.7° ± 3.7° (p = 0.67). Torsion in CDIF was 2.6° ± 0.8°; CCMP, 2.4° ± 0.6° and controls, 2.4° ± 0.5° (p = 0.63). Patients with Chagas disease have no abnormalities in torsional mechanics during its indeterminate and initial cardiomyopathy stages.

Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. Methods: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. Results: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 48 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). Conclusion: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.

Transforming growth factor β1 (TGF-β1) is an important mediator in Chagas disease. Furthermore, patients with higher TGF-β1 serum levels show a worse clinical outcome. Gene polymorphism may account for differences in cytokine production during infectious diseases. We tested whether TGFB1 polymorphisms could be associated with Chagas disease susceptibility and severity in a Brazilian population. We investigated five single-nucleotide polymorphisms (−800 G>A, −509 C>T, +10 T>C, +25 G>C, and +263 C>T). 152 patients with Chagas disease (53 with the indeterminate form and 99 with the cardiac form) and 48 noninfected subjects were included. Genotypes CT and TT at position −509 of the TGFB1 gene were more frequent in Chagas disease patients than in noninfected subjects. Genotypes TC and CC at codon +10 of the TGFB1 gene were also more frequent in Chagas disease patients than in noninfected subjects. We found no significant differences in the distribution of the studied TGFB1 polymorphisms between patients with the indeterminate or cardiac form of Chagas disease. Therefore, −509 C>T and +10 T>C TGFB1 polymorphisms are associated with Chagas disease susceptibility in a Brazilian population.

INTRODUCTION: We investigated the occurrence of coronary sinus abnormalities in the indeterminate form of Chagas disease (CD). METHODS: Differences between the maximum and minimum diameters of the coronary sinus (∆%) on echocardiography were evaluated in individuals with the indeterminate form of CD (n=14) and those without (n=16) CD. The association of the difference with abnormalities detected by echocardiography and myocardial scintigraphy was assessed. RESULTS: The mean Δ% values did not differ significantly between the groups. There was no correlation of the measurements with echocardiographic and myocardial scintigraphy findings. CONCLUSIONS: The coronary sinus evaluation revealed no differences between the groups.

Background Previous data has shown that patients in the indeterminate form of Chagas disease may present myocardial fibrosis as shown on through magnetic resonance imaging (MRI). However, there is little information available regarding the degree of severity of myocardial fibrosis in these individuals. This variable has the potential to predict the evolution of Chagas’ disease into its cardiac form. Objectives To describe the frequency and extent of myocardial fibrosis evaluated using an MRI in patients in the indeterminate form, and to compare it with other forms of the disease. Methods Patients were admitted one after another. Their clinical history was collected and they were submitted to laboratory exams and an MRI. Results Sixty-one patients with Chagas’ disease, with an average age of 58 ± 9 years old, 17 patients in the indeterminate form, 16 in the cardiac form without left ventricular (LV) dysfunction and 28 in the cardiac form with LV dysfunction were studied. P

Background Chagas disease (CD) is a frequent cause of dilated cardiomyopathy (CMP) in developing countries, leading to clinical heart failure and worse prognosis. Therefore, the development and evolution of this CMP has always been a major topic in numbers of previous studies. A comprehensive echocardiographic study of left ventricular (LV) mechanics, fully assessing myocardial contraction, has never been done before. This could help characterize and improve the understanding of the evolution of this prevalent CMP. Methods A total of 47 chagasic and 84 control patients were included in this study and allocated in groups according to LV ejection fraction. 2D-Echocardiogram was acquired for LV mechanics analysis by speckle tracking echocardiography. Results Mean age of chagasic individuals was 55y and 16 (34 %) were men. Significant difference was found in global longitudinal velocity analysis, with lower values in indeterminate form. In the group with severe systolic dysfunction, a paradoxical increase in longitudinal and apical radial displacements were demonstrated. In parallel, segmental analyzes highlighted lower values of radial displacement, strain and strain rate into inferior and inferolateral walls, with increase of these values in septal and anterior walls. Conclusion Chagasic CMP has a vicarious pattern of contraction in the course of its evolution, defined by reduced displacement and strain into inferior and posterior walls with paradoxical increase in septal and anterior segments. Also, lower longitudinal velocities were demonstrated in CD indeterminate form, which may indicate an incipient myocardial injury.

Between 1999-2002, Médécins Sans Frontières-Spain implemented a project seeking to determine the efficacy and safety of benznidazole in the treatment of recent chronic Chagas disease in a cohort of seropositive children in the Yoro Department, Honduras. A total of 24,471 children were screened for Trypanosoma cruzi IgG antibodies through conventional enzyme-linked immunosorbent assays (ELISA) on filter paper. Recombinant ELISA (0.93% seroprevalence) showed 256 initially reactive cases, including 232 confirmed positive cases. Of these, 231 individuals were treated with benznidazole (7.5 mg/kg/day) for 60 days and were followed with a strict weekly medical control and follow-up protocol. At the end of the project, 229 patients were examined by the Honduras Secretariat of Health for post-treatment serological assessments; 88.2% seroconverted after 18 months and 93.9% seroconverted after three years. No differences were found in the seroconversion rates according to age or sex. Most of the side effects of the treatment were minor. These results support the argument that in areas where T. cruzi I is predominant and in areas affected by T. cruzi II, when vector transmission has been interrupted, Chagas disease diagnosis and treatment are feasible, necessary and ethically indisputable.

Chagas' disease is a common cause of cardiac autonomic impairment. In an endemic area there is a predominance of the indeterminate form and the number of elderly individuals committed by the disease is increasing. This study aimed to investigate the profile of heart rate variability (HRV) in elderly chagasic patients. 28 aged chagasic (CH), 28 non-chagasic (NC) aged individuals and 28 adults between 20 and 40 years old (YG) were studied. R-R intervals were assessed in time and frequency domains applying an autoregressive algorithm. There was no difference regarding temporal and spectral indices among the elderly groups in baseline. The values of the variance in CH, NC and YG individuals were 891.80, 283.60, 2557.00, showing a reduction of the total HRV in the aged groups when compared to the young control (p < 0.001). During the cold face test, the pNN50 response was significantly different only in the young group (p < 0.001). The temporal and spectral indices were not different among the elderly groups. The percentile changes of the R-R intervals induced by the tilt test in CH, NC and YG were respectively -7.04%, -9.35%, -15.81%, being significantly higher in the young individuals (p < 0.001). There was no difference regarding the percentile changes of the temporal and spectral indices between CH and NC elderly patients. The cardiac autonomic function assessed by HRV parameters presented no differences among the elderly individuals (CH and NC) living in an endemic area.

Introduction Determining the genetic similarities among Trypanosoma cruzi populations isolated from different hosts and vectors is very important to clarify the epidemiology of Chagas disease. Methods An epidemiological study was conducted in a Brazilian endemic area for Chagas disease, including 76 chronic chagasic individuals (96.1% with an indeterminate form; 46.1% with positive hemoculture). Results T. cruzi I (TcI) was isolated from one child and TcII was found in the remaining (97.1%) subjects. Low-stringency single-specific-primer-polymerase chain reaction (LSSP-PCR) showed high heterogeneity among TcII populations (46% of shared bands); however, high similarities (80-100%) among pairs of mothers/children, siblings, or cousins were detected. Conclusions LSSP-PCR showed potential for identifying similar parasite populations among individuals with close kinship in epidemiological studies of Chagas disease.

Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and thus influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies has led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks.

OBJECTIVE: To identify and associate potential electrocardiographic and echocardiographic changes in patients with the indeterminate form of Chagas' disease during long-term follow-up. METHODS: One hundred sixty patients underwent standard electrocardiography and two-dimensional guided M-mode echocardiography for left ventricular ejection fraction determination. Patients were followed up for 98.6±30.4 months, undergoing repeat electrocardiographic studies at 6-month intervals and echocardiographic studies at 12-month intervals. RESULTS: Based on the electrocardiographic findings, the patients were divided into group I, 125 patients (78.6%) with normal electrocardiograms throughout follow-up, and group II, 34 patients (21.3%) who developed electrocardiographic changes. Group II was further divided into group IIA (9 patients, 5.6%) with permanent electrocardiographic changes, group IIB (14 patients, 8.8%) with transitory electrocardiographic changes, and group IIC (11 patients, 6.9%) with changes appearing only on the final electrocardiogram. Left ventricular ejection fractions remained normal in the entire population studied and did not differ among groups. CONCLUSION: The indeterminate form of Chagas' disease clearly represents a benign condition with a favorable long-term prognosis. Although some patients develop electrocardiographic changes, left ventricular systolic function is well preserved.

We studied the serum levels of IL-2, IFN-g and TNF in different clinical forms of Chagas' disease and in patients clinically compensated and decompensated. Cytokines measured in 91 patients with the chronic form of the disease did not differ from those of 13 normal individuals, suggesting the absence of activation of the TH1 pattern of lymphocyte response. There were no statistical differences among the 17 patients in the indeterminate form of the disease, the patients presenting either early (n = 4) or well-developed signs of cardiomyopathy (n = 62), the digestive (n = 4) or the mixed (n = 4) forms of the disease. Serum TNF was undetectable and IFN-g levels did not differ between clinical forms and severities of Chagas' disease. However, we found IL-2 higher levels in the 25 non-controlled patients than in the 66 controlled individuals (p < 0,001). We suggest that IL-2 dosage may be useful as an indicator of the need for more aggressive procedures. Estudamos os níveis séricos da IL-2, IFN-g e do TNF-a de portadores da doença de Chagas em suas diferentes formas clínicas, compensados e descompensados. As citocinas medidas nos 91 pacientes com a forma crônica da doença não diferiram dos níveis de 13 indivíduos controle. Não houve diferença estatística entre os 17 portadores da forma indeterminada da doença e os portadores de cardiopatia insipiente (n = 4), de cardiopatia bem estabelecida (n = 62), da forma digestiva (n = 4) ou da forma mista (n = 4) da doença. Os níveis séricos de TNF foram indetectáveis e IFN-g não diferiu nas diferentes formas clínicas ou com a severidade da doença. No entanto, encontramos níveis mais elevados de IL-2 nos 25 pacientes não-contrololados do que nos 66 pacientes bem compensados (p < 0,001). Sugerimos que a dosagem de IL-2 possa servir como indicadora da necessidade de terapêuticas mais agressivas nestes pacientes.

A forma indeterminada da doença de Chagas é definida pela presença de infecção pelo Trypanosoma cruzi na ausência de manifestações clínicas, radiológicas e eletrocardiográficas de acometimento cardíaco ou digestivo. Pacientes na forma indeterminada podem apresentar anormalidades cardiovasculares significativas à propedêutica mais avançada. Entretanto, a validade do conceito de forma indeterminada tem sido reafirmada, pela simplicidade diagnóstica e benignidade do prognóstico. Na prática clínica, dificuldades diagnósticas são freqüentes, relacionadas à subjetividade e ao significado incerto de achados clínicos, eletrocardiográficos e radiológicos. Adicionalmente, o prognóstico na forma indeterminada não é uniformemente bom: após cinco a 10 anos, postula-se que um terço dos pacientes evoluirão para a forma cardíaca. A morte súbita, uma complicação rara, pode ser a primeira manifestação da doença. É necessária uma reavaliação do conceito de forma indeterminada, com redefinição dos critérios diagnósticos e da conduta terapêutica. A estratificação do risco individual, através de métodos clínicos e não-invasivos, pode permitir o reconhecimento de grupos de risco aumentado, passíveis de intervenções terapêuticas. Como o tratamento etiológico pode prevenir o aparecimento da cardiopatia, seu papel no manejo da forma indeterminada deve ser reavaliado.

A forma indeterminada da doença de Chagas é definida pela presença de infecção pelo Trypanosoma cruzi na ausência de manifestações clínicas, radiológicas e eletrocardiográficas de acometimento cardíaco ou digestivo. Pacientes na forma indeterminada podem apresentar anormalidades cardiovasculares significativas à propedêutica mais avançada. Entretanto, a validade do conceito de forma indeterminada tem sido reafirmada, pela simplicidade diagnóstica e benignidade do prognóstico. Na prática clínica, dificuldades diagnósticas são freqüentes, relacionadas à subjetividade e ao significado incerto de achados clínicos, eletrocardiográficos e radiológicos. Adicionalmente, o prognóstico na forma indeterminada não é uniformemente bom: após cinco a 10 anos, postula-se que um terço dos pacientes evoluirão para a forma cardíaca. A morte súbita, uma complicação rara, pode ser a primeira manifestação da doença. É necessária uma reavaliação do conceito de forma indeterminada, com redefinição dos critérios diagnósticos e da conduta terapêutica. A estratificação do risco individual, através de métodos clínicos e não-invasivos, pode permitir o reconhecimento de grupos de risco aumentado, passíveis de intervenções terapêuticas. Como o tratamento etiológico pode prevenir o aparecimento da cardiopatia, seu papel no manejo da forma indeterminada deve ser reavaliado.The indeterminate form of Chagas' disease is defined by the absence of clinical, radiological and electrocardiographic manifestations of cardiac or digestive involvement in Trypanosoma cruzi chronic infected persons. When submitted to advanced cardiovascular tests, these patients may present significant abnormalities. However, the indeterminate form concept was reaffirmed as valid, since diagnostic criteria are simple and prognosis is benignant. In clinical practice, diagnostic difficulties are frequent, related to subjectivity and uncertain meaning of clinical, electrocardiographic and radiological findings. Moreover, indeterminate form prognosis is not equally good: after five to 10 years, a third of patients will have cardiopathy. Sudden death, a rare complication, may be the first manifestation of Chagas' disease. It is necessary to reappraise indeterminate form concept, redefining diagnostic criteria and therapeutic management. Clinical and noninvasive evaluation may allow individual risk stratification; therapeutic interventions may be beneficial in high risk groups. Since etiologic treatment may prevent cardiopathy, its role in indeterminate form management must be reassessed.

Objetivou-se avaliar as alterações do esfíncter superior esofágico pela eletromanometria em 37 pacientes portadores da forma clínica indeterminada da doença de Chagas. Foram encontrados 18 (48,6%) pacientes portadores de ondas sincrônicas. A média das pressões máximas do esfíncter foi significativamente maior entre os portadores de ondas sincrônicas. Assim, alguns indivíduos portadores da forma indeterminada da doença de Chagas possuem alterações funcionais caracterizadas pelo aumento da pressão do esfíncter superior do esôfago, que podem ser detectadas à eletromanometria. The objective was to study the disorders of upper esophageal sphincter in 37 patients with indeterminate clinical form of Chagas' disease. Eighty (48.6%) patients with synchronic waves were found. The average maximum pressure value of the upper esophageal sphincter was significantly higher in the synchronic group. Subjects with indeterminate clinical form of Chagas' disease may have functional disorders demonstrated by an increase in the pressure of the upper esophageal sphincter.

We read with interest the article by Sabino et al,1 who show a difference in the rate of progression to cardiomyopathy of 1.85% per year among 499 initially asymptomatic Trypanosoma cruzi –seropositive blood donors compared with 488 T cruzi –seronegative individuals (control group). That is, in a 1-year period, of 100 patients with the indeterminate form of Chagas disease, ≈2 patients will develop some cardiac alteration that is exclusively attributable to T cruzi infection. However, the study has some limitations …

Objective The objective was to evaluate the perceived quality of life of adult and older adult patients with different clinical forms of Chagas disease. Methods This descriptive and cross-sectional research was conducted between 2005 and 2008. Data were collected from 202 patients. The World Health Organization Quality of Life- -BREF was used to assess the quality of life domains. Statistical analyses included descriptive analysis, and univariate and multivariate logistic regression analyses. Results Of the 202 interviewed patients, 53.96% were female; 68.81% were aged £60 years, 66.83% presented the cardiac form, 11.39% presented the digestive form, and 21.78% had the indeterminate form. Patients with the cardiac and digestive forms were more likely to report lower quality of life in the physical, psychological, and social relationships domains than those with the indeterminate form. In the environment domain, women and those with more comorbidities had lower scores. Conclusion The social relationships domain received the highest scores, followed by the psychological and physical domains. The environment domain received the lowest scores. Comparing the scores of the World Health Organization Quality of Life-BREF domains by age group (adults and older adults) in relation to the clinical form, gender, and number of comorbidities, quality of life did not differ significantly in any of the study subgroups. Keywords : Aged. Chagas disease. Quality of life.

We performed a critical study of conventional serology, followed by supplementary serological, parasitological, and molecular tests, to assess the response to etiologic treatment of Chagas' disease. A group of 94 Chagas' disease patients treated with benznidazole at least 10 years earlier were evaluated from the laboratory and clinical points of view. When conventional serology (enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IIF], and indirect hemagglutination [IHA]) and classic criteria (consistent results with any two of the three tests) or more rigorous criteria (consistent results from the three tests) were used, 10.6% and 8.5% of patients were considered treated and cured (TC) by classic and rigorous criteria, respectively. Patients were then evaluated using supplementary (recombinant ELISA andTrypanosoma cruziexcreted-secreted antigen blotting [TESA-blot]), parasitological (hemoculture), and molecular (PCR) tests. The results of recombinant ELISA were similar to those with the rigorous criterion (three consistent test results). The TESA-blot group showed a higher percentage (21.3%) of negative results than the groups defined by either cure criterion. Hemoculture and PCR gave negative results for all treated and cured (TC) patients, regardless of the criterion used. Recombinant ELISA and TESA-blot tests showed negative results for 70% and 87.5% of the patients categorized as TC by the classic and three-test criteria, respectively. For patients with discordant conventional serology, the supplementary serological and molecular tests were the decisive factor in determining therapeutic failure. Clinical evaluation showed that 62.5% of TC patients presented with the indeterminate form of the disease. Additionally, treated patients with negative TESA-blot results should be reevaluated later with all methodologies used here to verify whether TESA-blot is a reliable way to determine early parasitological cure of Chagas' disease.

The morphologic features of the indeterminate and the chronic cardiac forms of Chagas' disease, and their clinicai correlations, are briefly reviewed. The significance of mild focal myocarditis as the main change of the indeterminate form, the myocardial inflammation and flbrosis of the chronic cardiac form, pius the mvolvement of the conducting system, are particularly considered.

Background Assessment of myocardial deformation in Chagas disease may help us to better understand the disease pathophysiology and to detect early myocardial involvement. We aimed to characterize myocardial deformation in patients in different forms of Chagas disease and, specifically, assess differences between patients in the indeterminate form and controls. Methods and Results Speckle tracking echocardiography was performed in 98 subjects (22 with Chagas cardiomyopathy, 32 in the indeterminate form, and 44 control subjects) to quantify global and segmental left ventricular (LV) radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). In a subset of patients from the indeterminate and control groups (n = 25), LV peak systolic twist and untwisting velocities were additionally assessed. Global RS, CS, and LS showed a significant decreasing trend across groups. Patients in the indeterminate form had significantly lower global RS and RS in the midinferior segment (median 39.8% vs 49.3% [ P = .046] and 44.0% vs 56.0% [ P = .038], respectively) and lower twist and untwisting velocity ( P Conclusion Evaluation of myocardial deformation, particularly of RS, appears to be a sensitive technique for detection of myocardial involvement in patients in the indeterminate form and provides insights into the still unrevealed pathophysiology of Chagas heart involvement.

Publisher Summary In spite of the progress achieved, there are a number of future challenges to pursue the way ahead. They can be divided into three categories: epidemiological, technical, and political. Chagas disease is named after Carlos Chagas, the pioneer researcher who first described it in 1909. Existing only on the American continent, the disease is caused by a flagellate parasite, Trypanosoma cruzi, and is primarily transmitted to humans by blood-sucking triatomine bugs and by blood transfusion. Chagas disease has two successive phases, acute and chronic. The acute phase lasts 6–8 weeks. Once the acute phase subsides, most of the infected patients recover an apparent healthy status, where no organ damage can be demonstrated by the current standard methods of clinical diagnosis. The infection can only be verified by serological or parasitological tests. This form of the chronic phase of Chagas disease is called indeterminate form. Most patients remain in this form of the disease. However, after several years of the chronic phase, 20–35% of the infected individuals, depending on the geographical area, develop irreversible lesions of the autonomous nervous system in the heart, esophagus, colon, and peripheral nervous system.

Com o objetivo de avaliar a apresentação clínica da doença de Chagas em idosos foi realizado estudo retrospectivo utilizando-se os prontuários de doentes atendidos em ambulatório de referência. A casuística foi dividida em idosos (> 60 anos) e não idosos. Avaliou-se: sexo, co-morbidades, forma clínica, eletrocardiograma e títulos das sorologias. Idosos (61 casos): média de idade de 66,0 ± 5 anos, 67,2% do sexo feminino; comorbidades em 59%, mais freqüente a hipertensão arterial sistêmica (HAS)= 39,3%; forma indeterminada= 1,6%, forma cardíaca= 88,5%, forma digestiva= 36,1%; alterações freqüentes no eletrocardiograma: bloqueio divisional ântero-superior esquerdo (BDASE)= 41%, bloqueio completo de ramo direito (BCRD)= 32,8%, extra-sístole ventricular (EV)=22,9%. Não idosos (61 casos): média de idade: 39,30±8,36 anos, 54,1% do sexo feminino; comorbidades em 50,8%, mais freqüente a HAS (26,2%); forma indeterminada= 18% (p 60 years old) and non-elderly. Sex, comorbidities, clinical form, electrocardiogram and serological titers were evaluated. In the elderly group (61 cases), the mean age was 66.03 ± 5 years; 67.2% were female; 59% presented comorbidities (most frequently systemic arterial hypertension, in 39.3%); 1.6% had the indeterminate clinical form, 88.5% the cardiac form and 36% the digestive form; and abnormalities were frequently found on electrocardiograms: 41% presented anterosuperior left bundle branch block (AS-LBBB), 32.8% presented right bundle branch block (RBBB) and 22.9% presented ventricular ectopic beats (VEB). In the non-elderly group (61 cases), the mean age was 39.30 ± 8.36 years; 54.1% were female; 50.8% presented comorbidities (most frequently systemic arterial hypertension, in 26.2%); 18% had the indeterminate clinical form (p

Este trabalho descreveu o perfil clínico-epidemiológico de pacientes com doença de Chagas atendidos no ambulatório e na internação do Hospital Universitário de Maringá (HUM), Paraná, Brasil, entre maio de 1998 a maio de 2003. A média de idade foi maior no serviço de internação (p < 0,000). O sexo masculino predominou entre os internados e o feminino entre os ambulatoriais (p = 0,0033). De 95 pacientes, 60% nasceram em Minas Gerais e São Paulo e 25,3% no Paraná. A história familiar para doença de Chagas foi positiva em 68,9% deles e 53,3% relataram a presença de triatomíneos no domicílio. Em ordem decrescente ocorreram as formas clínicas cardíaca, digestiva, indeterminada e cardiodigestiva. A forma indeterminada prevaleceu entre os ambulatoriais e as formas cardíaca e digestiva entre os internados. As complicações crônicas cardíacas e digestivas foram as principais queixas para a internação. Destacam-se os altos percentuais de doença cardíaca (38,9%) e digestiva (26,3%) encontrados neste estudo, de forma distinta ao que acontece em outras regiões geográficas. O HUM disponibiliza o tratamento sintomático dessas complicações e não prioriza o tratamento etiológico mesmo para pacientes em fase indeterminada. This paper describes the clinical and epidemiological profile of patients with Chagas disease treated in outpatient and inpatient departments at the Maringá University Hospital (UHM) in Paraná State, Brazil, from May 1998 to May 2003. Mean age was higher among hospitalized patients (p < 0.000). Hospitalized patients were predominantly males, as opposed to inpatients who were mostly females (p = 0.0033). Of the 95 patients, 60% were born in the States of Minas Gerais and São Paulo and 25.3% in Paraná. Family history for Chagas was positive in 68.9%, while 53.3% reported the presence of triatomine vectors in the household. In decreasing order, the most common clinical forms were cardiac, digestive, indeterminate, and cardiodigestive. The indeterminate form predominated among outpatients, as opposed to the cardiac and digestive forms among inpatients. Chronic cardiac and digestive complications were the principal complaints at hospital admission. This study showed particularly high percentages of cardiac (38.9%) and digestive disease (26.3%) as compared to other geographic areas. The Maringá University Hospital provides symptomatic care for these complications and does not prioritize etiological treatment, even for patients in the indeterminate phase.

Background Chagas disease patients with right bundle-branch block (RBBB) have diverse clinical presentation and prognosis, depending on left ventricular (LV) function. Autonomic disorder can be an early marker of heart involvement. The heart rate recovery (HRR) after exercise may identify autonomic dysfunction, with impact on therapeutic strategies. This study was designed to assess the HRR after symptom-limited exercise testing in asymptomatic Chagas disease patients with RBBB without ventricular dysfunction compared to patients with indeterminate form of Chagas disease and healthy controls. Methods One hundred and forty-nine subjects divided into 3 groups were included. A control group was comprised of healthy individuals; group 1 included patients in the indeterminate form of Chagas disease; and group 2 included patients with complete RBBB with or without left anterior hemiblock, and normal ventricular systolic function. A symptom-limited exercise test was performed and heart rate (HR) response to exercise was assessed. HRR was defined as the difference between HR at peak exercise and 1 min following test termination. Results There were no differences in heart-rate profile during exercise between healthy individuals and patients in indeterminate form, whereas patients with RBBB had more prevalence of chronotropic incompetence, lower exercise capacity and lower HRR compared with patients in indeterminate form and controls. A delayed decrease in the HR after exercise was found in 17 patients (15%), 9% in indeterminate form and 24% with RBBB, associated with older age, worse functional capacity, impaired chronotropic response, and ventricular arrhythmias during both exercise and recovery. By multivariable analysis, the independent predictors of a delayed decrease in the HRR were age (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.03 to 1.21; p = 0.010) and presence of RBBB (OR 3.97; 95% CI 1.05 to 15.01; p = 0.042). Conclusions A small proportion (15%) of asymptomatic Chagas patients had attenuated HRR after exercise, being more prevalent in patients with RBBB compared with patients in indeterminate form and controls.

Doze pacientes com idades entre 7 a 12 anos, na forma indeterminada da doença de Chagas, com sorologia e xenodiagnóstico positivos, receberam tratamento específico. Dois pacientes tomaram 7mg/kg de nifurtimox durante 60 e 90 dias e 10 usaram 5-7mg/kg de benznidazol durante 60 dias. A evolução clínica foi verificada através de exame clínico, eletrocardiograma, exame radiológico contrastado do esôfago. Após o tratamento somente uma (8,3%) paciente apresentou todos os exames negativos. Oito deles foram avaliados após oito anos do tratamento e 4 acompanhados durante 20 anos. Sete (58,4%) permaneceram na forma indeterminada e 4 (33,3%) chagásicos progrediram clinicamente para cardiopatia grau II e/ou esofagopatia, apesar do tratamento precoce. São necessários estudos com maior número de crianças na fase indeterminada e acompanhamento a longo prazo para se estabelecer a influência do tratamento específico na evolução da doença de Chagas. Twelve chagasic patients between the ages of seven and twelve, in the indeterminate phase with serology and xenodiagnosis positive, received the specific treatment. Eight of these were evaluated after an eight-year treatment period and four were followed-up during 20 years. Two patients took 7mg/kg of nifurtimox during sixty and ninety days and ten of these used 5-7mg/kg of benznidazole during 60 days. The clinical outcome was verified through clinical examination, electrocardiogram and contrasted X-ray of the esophagus. After the treatment, only one patient presented negativity in all the examinations. Seven (58.4%) remained in the indeterminate form and despite the precocious treatment four chagasic patients (33.3%) progressed clinically to second degree cardiopathy and/or megaesophagus.

The objective was to study the disorders of upper esophageal sphincter in 37 patients with indeterminate clinical form of Chagas’ disease. Eighty (48.6%) patients with synchronic waves were found. The average maximum pressure value of the upper esophageal sphincter was significantly higher in the synchronic group. Subjects with indeterminate clinical form of Chagas’ disease may have functional disorders demonstrated by an increase in the pressure of the upper esophageal sphincter.

A forma indeterminada da doença de Chagas é definida pela presença de infecção pelo Trypanosoma cruzi na ausência de manifestações clínicas, radiológicas e eletrocardiográficas de acometimento cardíaco ou digestivo. Pacientes na forma indeterminada podem apresentar anormalidades cardiovasculares significativas à propedêutica mais avançada. Entretanto, a validade do conceito de forma indeterminada tem sido reafirmada, pela simplicidade diagnóstica e benignidade do prognóstico. Na prática clínica, dificuldades diagnósticas são freqüentes, relacionadas à subjetividade e ao significado incerto de achados clínicos, eletrocardiográficos e radiológicos. Adicionalmente, o prognóstico na forma indeterminada não é uniformemente bom: após cinco a 10 anos, postula-se que um terço dos pacientes evoluirão para a forma cardíaca. A morte súbita, uma complicação rara, pode ser a primeira manifestação da doença. É necessária uma reavaliação do conceito de forma indeterminada, com redefinição dos critérios diagnósticos e da conduta terapêutica. A estratificação do risco individual, através de métodos clínicos e não-invasivos, pode permitir o reconhecimento de grupos de risco aumentado, passíveis de intervenções terapêuticas. Como o tratamento etiológico pode prevenir o aparecimento da cardiopatia, seu papel no manejo da forma indeterminada deve ser reavaliado. The indeterminate form of Chagas' disease is defined by the absence of clinical, radiological and electrocardiographic manifestations of cardiac or digestive involvement in Trypanosoma cruzi chronic infected persons. When submitted to advanced cardiovascular tests, these patients may present significant abnormalities. However, the indeterminate form concept was reaffirmed as valid, since diagnostic criteria are simple and prognosis is benignant. In clinical practice, diagnostic difficulties are frequent, related to subjectivity and uncertain meaning of clinical, electrocardiographic and radiological findings. Moreover, indeterminate form prognosis is not equally good: after five to 10 years, a third of patients will have cardiopathy. Sudden death, a rare complication, may be the first manifestation of Chagas' disease. It is necessary to reappraise indeterminate form concept, redefining diagnostic criteria and therapeutic management. Clinical and noninvasive evaluation may allow individual risk stratification; therapeutic interventions may be beneficial in high risk groups. Since etiologic treatment may prevent cardiopathy, its role in indeterminate form management must be reassessed.

Purpose: Up to 20 to 30% of chronic Chagas' disease patients are expected to develop the cardiac form of the disease. The identification of left ventricular (LV) diastolic dysfunction or left atrial (LA) dysfunction may yield a strategy to recognize early cardiac involvement. Our aim was to analyze these parameters in Chagas' disease patients with normal LV systolic function using new echocardiographic techniques. Methods: Echocardiograms from 52 Chagas' disease patients with the indeterminate form, 29 patients at the stage A of the cardiac form (changes limited to the electrocardiogram) and 25 controls were consecutively acquired. LV diastolic function was analyzed by interrogation of the mitral inflow, pulmonary vein flow, color M-mode flow propagation velocity, LV untwist and tissue Doppler of the mitral annulus. LA function was analyzed by real-time 3 dimensional echocardiography and LA strain (ɛ) analysis including global peak positive LA ɛ (ɛ pos peak), peak negative LA ɛ and total LA ɛ. Results: All groups presented similar age, gender distribution, chamber diameters, LV mass and LV systolic function. Diastolic dysfunction was more prevalent in stage A patients. While all controls presented normal LV diastolic function, 11.5% of the patients with the indeterminate form presented delayed relaxation and 2% pseudo-normal LV diastolic function and 35.5% of the patients at the stage A of the cardiac form presented delayed relaxation and 13.5% pseudo-normal LV diastolic function (p=0.0001). Tissue Doppler was the best index to discriminate the presence of diastolic dysfunction. E/E' ratio was progressively higher (C: 5.8±1.6; indeterminate: 7.0±1.7; stage A: 8.0±2.9; p=0.0008) and E'/A' ratio was progressively lower (C: 1.5±0.3; indeterminate: 1.2±0.5; stage A: 1.0±0.3; p=0.0004) from controls towards stage A patients. LA volumes were higher in stage A patients than in controls, but LA emptying fractions did not differ among the groups. LA ɛ pos peak was lower in stage A patients (15.1±4.2%) than in patients with the indeterminate form (17.9±4.8%) and controls (17.8±4.3%; p=0.02), while the other LA ɛ parameters did not differ among the groups. Conclusions: Patients with Chagas' disease and normal LV systolic function present LV diastolic dysfunction, which is more prevalent in patients at the stage A of the cardiac form. Tissue Doppler was the best index to discriminate the presence of diastolic dysfunction and routine evaluation of E'/A' ratio may enable its early recognition. Depression of LA conduit function in stage A patients was observed only by LA strain analysis.