Indeterminate Form Of Chagas Disease Research Articles

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

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. 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. 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. [https://ensaiosclinicos.gov.br/rg/RBR-10yxgcr9/], identifier [U1111-1263-0153].

Chagas Disease Megaesophagus Patients Carrying Variant MRPS18B P260A Display Nitro-Oxidative Stress and Mitochondrial Dysfunction in Response to IFN-γ Stimulus.

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, affects 8 million people, and around 1/3 develop chronic cardiac (CCC) or digestive disease (megaesophagus/megacolon), while the majority remain asymptomatic, in the indeterminate form of Chagas disease (ASY). Most CCC cases in families with multiple Chagas disease patients carry damaging mutations in mitochondrial genes. We searched for exonic mutations associated to chagasic megaesophagus (CME) in genes essential to mitochondrial processes. We performed whole exome sequencing of 13 CME and 45 ASY patients. We found the damaging variant MRPS18B 688C > G P230A, in five out of the 13 CME patients (one of them being homozygous; 38.4%), while the variant appeared in one out of 45 ASY patients (2.2%). We analyzed the interferon (IFN)-γ-induced nitro-oxidative stress and mitochondrial function of EBV-transformed lymphoblastoid cell lines. We found the CME carriers of the mutation displayed increased levels of nitrite and nitrated proteins; in addition, the homozygous (G/G) CME patient also showed increased mitochondrial superoxide and reduced levels of ATP production. The results suggest that pathogenic mitochondrial mutations may contribute to cytokine-induced nitro-oxidative stress and mitochondrial dysfunction. We hypothesize that, in mutation carriers, IFN-γ produced in the esophageal myenteric plexus might cause nitro-oxidative stress and mitochondrial dysfunction in neurons, contributing to megaesophagus.

Intra-Discrete Typing Unit TcV Genetic Variability of Trypanosoma cruzi in Chronic Chagas' Disease Bolivian Immigrant Patients in Barcelona, Spain.

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.

Indeterminate form of Chagas disease: historical, conceptual, clinical, and prognostic aspects

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.

Early impairment of myocardial deformation assessed by regional speckle-tracking echocardiography in the indeterminate form of Chagas disease without fibrosis detected by cardiac magnetic resonance.

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.

Speckle tracking echocardiography in the indeterminate form of Chagas disease.

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. 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. 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. 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). 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.

Risk of Chronic Cardiomyopathy Among Patients With the Acute Phase or Indeterminate Form of Chagas Disease

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. To estimate the risk of developing chronic cardiomyopathy in patients with acute and indeterminate chronic forms of Chagas disease. 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. 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. 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 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. 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. 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.

Radionuclide esophageal transit scintigraphy in chronic indeterminate and cardiac forms of Chagas disease.

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. 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). 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 <0.001). The lowest median ETT was observed for the controls (median = 8.0), followed by indeterminate form (median = 16.5) and DCCh (median = 60.0). Regarding %EE, a higher median value was observed for the controls (median = 92.3), followed by indeterminate form (median = 86.7) and DCCh (median = 56.9). In the DCCh group, ETT and %EE were significantly correlated with LVEF values (r = 0.398; P = 0.015) and (r = 0.475; P = 0.003), respectively. An association between left ventricular systolic dysfunction and functional esophageal alterations was observed which was interpreted as indirect evidence of concomitance of gastrointestinal and cardiac disorders. We also found that the greater the impairment of the esophagus's autonomic function, the worse the cardiac dysfunction.

Risk of Chronic Cardiomyopathy Development and Its Determinants in Patients with the Acute Phase and Indeterminate Form of Chagas Disease: A Systematic Review and Meta-Analysis

Risk of Chronic Cardiomyopathy Development and Its Determinants in Patients with the Acute Phase and Indeterminate Form of Chagas Disease: A Systematic Review and Meta-Analysis

P1568 Echocardiographic changes and ventricular mechanics in the indeterminate form of chagas disease

Abstract 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 &amp;lt;5%. Results Demographic data (age, body surface area) with no significant differences. Left ventricular (LV) diameters (p &amp;lt;0.0001), septal thickness (p = 0.01), mass index (p &amp;lt;0.0001) and diameters and indexed volume of left atrium (LA) were higher in Chagas patients (p &amp;lt;0.0001). Left ventricular ejection fraction (EF) showed no significant difference between groups. The mitral E wave velocity showed no significant difference, but the e" wave velocity of tissue Doppler (p = 0.02) and the E/e" ratio (p = 0.002) were higher in Chagas patients. Global longitudinal strain (GLS) (p &amp;lt;0.0001) and mechanical dispersion of the LV (p &amp;lt;0.0001) were lower in Chagas patients. Basal right ventricular (RV) diameter, tricuspid annulus excursion (TAPSE) and tricuspid regurgitation velocity did not show differences and fractional area change of the RV (p = 0.03) was lower in Chagas patients. Longitudinal strain of the RV free wall (p = 0.01) was lower in Chagas patients and mechanical dispersion of RV (p =0.002) was higher. 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.

Echocardiographic Study of the Coronary Sinus in the Indeterminate Form of Chagas Disease.

We investigated the occurrence of coronary sinus abnormalities in the indeterminate form of Chagas disease (CD). 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. The mean Δ% values did not differ significantly between the groups. There was no correlation of the measurements with echocardiographic and myocardial scintigraphy findings. The coronary sinus evaluation revealed no differences between the groups.

Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation-A histopathological study.

Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective invivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short- and long-term treatment. In the present study, we induced the indeterminate form of Chagas disease in mice with a Y strain of Trypanosoma cruzi and analysed the histopathological data about the effects of NFOH and BZN on different tissues, including the heart, skeletal muscle, liver, kidney, colon, spleen and brain. After infection, BALB/c mice were treated with NFOH (150mg/kg) and BZN (60mg/kg) for 60days and then submitted to immunosuppression using dexamethasone (5mg/kg) for 14days. Two trained analysts, as part of a blind evaluation, examined the results using serial sections of 3mm diameter in two different moments. The results showed reactivation of the disease only in the infected nontreated group (POS). After treatment, amastigote nests were found in the heart, colon, liver and skeletal muscle in the POS group and in the heart and liver of the BZN group. Interestingly, amastigote nests were not found in the NFOH and NEG groups. The histopathological analysis showed fewer tissue lesions and parasite infiltrates in the NFOH group when compared with the BZN and POS groups. We have not observed any increase in the levels of hepatocellular injury biomarkers (AST/ALT) in the NFOH group. These invivo studies show the potential for NFOH as an effective and safe compound useful as an anti-T.cruzi agent.

The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas' Disease: A Study Using Magnetic Resonance.

BackgroundPrevious 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.ObjectivesTo 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.MethodsPatients were admitted one after another. Their clinical history was collected and they were submitted to laboratory exams and an MRI.ResultsSixty-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 <0.05 was considered to be statistically significant. Late enhancement was detected in 37 patients (64%). Myocardial fibrosis was identified in 6 individuals in indeterminate form (41%; 95% CI 23-66) in a proportion similar to that observed in cardiac form without LV dysfunction (44%); p = 1.0. Among the individuals with fibrosis, the total area of the affected myocardium was 4.1% (IIQ: 2.1 - 10.7) in the indeterminate form versus 2.3% (IIQ: 1-5) in the cardiac form without LV (p = 0.18). The left ventricular fraction ejection in subjects in the indeterminate form was similar to that of the individuals in the cardiac form without ventricular dysfunction (p = 0.09).ConclusionThe presence of fibrosis in the indeterminate form of Chagas’ disease has a frequency and extension similar to that of in the cardiac form without dysfunction, suggesting that the former is part of a subclinical disease spectrum, rather than lacking cardiac involvement.

Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease.

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. 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. 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. 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.

Evaluation of P2X7 receptor expression in peripheral lymphocytes and immune profile from patients with indeterminate form of Chagas disease.

Chagas disease (CD) is caused by Trypanosoma cruzi, an intracellular protozoan which is a potent stimulator of cell-mediated immunity. In the indeterminate form of CD (IFCD) a modulation between pro- and anti-inflammatory responses establishes a host-parasite adaptation. It was previously demonstrated that purinergic ecto-enzymes regulates extracellular ATP and adenosine levels, influencing immune and inflammatory processes during IFCD. In inflammatory sites ATP, as well as its degradation product, adenosine, function as signaling molecules and immunoregulators through the activation of purinergic receptors. In this work, it was analyzed the gene and protein expression of P2X7 purinergic receptor in peripheral lymphocytes and serum immunoregulatory cytokines from IFCD patients. Gene and protein expression of P2X7 receptor (P2X7R), and serum cytokines (IL-2, IL-10, IL-17 and IFN-γ) were unaltered. However, IFCD group showed significantly higher IL-4 and IL-6 levels while TNF-α was significantly decreased. These results indicate that imune profile of IFCD patients displays anti-inflammatory characteristics, consistent with the establishment of an immunomodulatory response. Further study about the molecular knowledge of P2X7R in IFCD is useful to clarify the participation of purinergic system in the regulatory mechanism which avoid the progression of CD.

Indeterminate form of Chagas disease: is left ventricular torsional mechanics a clue to subclinical myocardial abnormalities?

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 55years, five (24%) men, and controls, 50years, 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.

Trypanosoma cruzi III causing the indeterminate form of Chagas disease in a semi-arid region of Brazil

Trypanosoma cruzi is subdivided into six discrete typing units (DTUs), TcI-TcVI. The precise identification of each can contribute to tracking wild DTUs that invade the domiciliary environment. Twenty T. cruzi stocks isolated from 16 chagasic patients, two Panstrongylus lutzi, one Galea spixii, and one Euphractus sexcinctus, from different localities in the State of Rio Grande do Norte, Brazil, were characterized by genotyping the 3' region of the 24Sα rRNA gene, the mitochondrial cytochrome oxidase subunit 2 gene, and the spliced leader intergenic region. TcIII was identified in 18.7% (3/16) of patients from different municipalities, as well as in P. lutzi, G. spixii, and E. sexcinctus, indicating the connection between the sylvatic and domestic cycles in this Brazilian semi-arid region. TcI and TcII were also detected, in 37.5% (6/16) and 43.8% (7/16) of patients, respectively. These DTUs were associated with cardiac, digestive, and indeterminate clinical forms, while TcIII was identified only in patients with the indeterminate form. The occurrence of these DTUs reveals important phylogenetic diversity in T. cruzi isolates from humans. TcIII is reported for the first time in northeastern Brazil. These findings appear to indicate an overlap between the sylvatic and domestic transmission cycles of the parasite in this region.

Heart rate recovery in asymptomatic patients with Chagas disease.

BackgroundChagas 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.MethodsOne 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.ResultsThere 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).ConclusionsA 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.

Left Atrial and Left Ventricular Diastolic Function in Chronic Chagas Disease

Left atrial (LA) and left ventricular (LV) diastolic function analysis can yield new strategies to recognize early cardiac involvement and prognostic indicators in Chagas disease. Patients with Chagas disease with the indeterminate (n= 69) or with the cardiac form (32 with changes limited to electrocardiography [stage A], 25 with changes in LV systolic function but no heart failure [HF; stage B], and 26 with HF) underwent evaluation of LV diastolic function (mitral inflow, pulmonary vein flow, color M-mode echocardiography, and tissue Doppler analysis), and LA function by three-dimensional echocardiography and strain analysis and were prospectively followed for the occurrence of clinical events. Echocardiograms were also obtained from 32 controls. LV diastolic dysfunction was gradually more prevalent and severe across groups from patients with the indeterminate form of Chagas disease to patients with HF. Tissue Doppler was the best tool to demonstrate the worsening of LV diastolic function across the groups (E' velocity: controls, 12.6 ± 2.3 cm/sec; patients with the indeterminate form, 12.1 ± 3.1 cm/sec; stage A, 10.3 ± 2.9 cm/sec; stage B, 8.3 ± 2.8cm/sec; patients with HF, 5.6 ± 1.9; P < .0001). Although maximum LA volume was increased only in patients with HF, minimum LA volume (controls, 8 ± 2 mL/m(2); patients with the indeterminate form, 8 ± 2 mL/m(2); stage A, 9 ± 3 mL/m(2); stage B, 11 ± 4 mL/m(2); patients with HF, 27 ± 17 mL/m(2); P < .0001) and precontraction LA volume (controls, 11 ± 3 mL/m(2); patients with the indeterminate form, 12 ± 3 mL/m(2); stage A, 13 ± 4mL/m(2); stage B, 16 ± 5 mL/m(2); patients with HF, 32 ± 19 mL/m(2); P < .0001) were increased in all cardiac form groups. LA conductive function was depressed in all cardiac form groups, while LA contractile function was depressed only in patients with HF. Cox proportional-hazards regression analysis revealed that end-systolic LV diameter (hazard ratio, 1.6; 95% confidence interval, 0.9-2.8; P= .09), E' velocity (hazard ratio, 0.5; 95% confidence interval, 0.3-0.8; P= .001), and peak negative global LA strain (hazard ratio, 1.21; 95% confidence interval, 1.02-1.4; P= .03), were independent predictors of clinical events. LV diastolic dysfunction was found in all forms of chronic Chagas disease, including those without LV systolic dysfunction. LV diastolic dysfunction may contribute to changes in LA volume and conductive function found in early stages of the cardiac form. Both LV diastolic function and LA contractile function were independent predictors of clinical events.

Letter by Rassi and Rassi Regarding Article, “Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic, Trypanosoma cruzi –Seropositive Former Blood Donors”

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 …