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

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

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

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

Benznidazole decreases the risk of chronic Chagas disease progression and cardiovascular events: A long-term follow up study.

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.

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

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

Cholinesterase inhibition reduces arrhythmias in asymptomatic Chagas disease.

INTRODUCTION: Parasympathetic dysfunction may play a role in the genesis of arrhythmias in Chagas disease. AIM: This study evaluates the acute effects of pyridostigmine (PYR), a reversible cholinesterase inhibitor, on the occurrence of arrhythmias in patients with Chagas cardiac disease. METHOD: Following a double-blind, randomized, placebo-controlled, cross-over protocol, 17 patients (age 50±2 years) with Chagas cardiac disease type B underwent 24-hour Holter recordings after oral administration of either pyridostigmine bromide (45 mg, 3 times/day) or placebo (PLA). RESULTS: Pyridostigmine reduced the 24-hours incidence (median [25%-75%]) of premature ventricular beats-PLA: 2998 (1920-4870), PYR: 2359 (940-3253), P=.044; ventricular couplets-PLA: 84 (15-159), PYR: 33 (6-94), P=.046. Although the total number of nonsustained ventricular tachycardia in the entire group was not different (P=.19) between PLA (1 [0-8]) and PYR (0 [0-4]), there were fewer episodes under PYR in 72% of the patients presenting this type of arrhythmia (P=.033). CONCLUSION: Acute administration of pyridostigmine reduced the incidence of nonsustained ventricular arrhythmias in patients with Chagas cardiac disease. Further studies that address the use of pyridostigmine by patients with Chagas cardiac disease under a more prolonged follow-up are warranted.

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

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

Effects of omega-3 polyunsaturated fatty acid supplementation in patients with chronic chagasic cardiomyopathy: study protocol for a randomized controlled trial.

BACKGROUND: Chronic chagasic cardiomyopathy is an inflammatory disease that occurs in approximately 30% of patients infected by the protozoan Trypanosoma cruzi, and it has a profile of high morbidity and mortality. The worst prognosis and the progression of this cardiomyopathy are associated with an exacerbated immune response and the production of proinflammatory cytokines, which also occur in other cardiomyopathies. Some nutrients, including omega-3 polyunsaturated fatty acids (PUFAs), promote the inhibition and/or stimulation of cytokine production. The objective of this trial is to study the effects of omega-3 PUFA supplementation on the inflammatory response and lipid profile in patients with chronic chagasic cardiomyopathy. METHODS/DESIGN: This is a parallel, randomized, placebo-controlled, double-blind clinical trial with 40 patients that will be conducted at a reference unit for Chagas disease patients, where the patients will be selected. The study will include patients with chronic chagasic cardiomyopathy who are 18 years of age or older. The exclusion criteria are (a) ongoing diarrheal disease, (b) inflammatory bowel disease, (c) diabetes or other endocrine disease, (d) use of fibrates, niacin, or statins, (e) use of anti-inflammatory drugs, (f) pregnant and lactating women, (g) use of vitamin, mineral, or omega-3 supplementation during the previous 30 days, (h) hospital admission during the study, and (i) other associated cardiomyopathies. The intervention will be treatment with omega-3 PUFAs at a dose of 3 g/day for 8 weeks, compared to placebo (corn oil). The primary endpoints will be the concentrations of inflammatory markers (interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ, and transforming growth factor (TGF)ß). Secondary endpoints will be the fasting glucose, lipid, and anthropometric profiles. For statistical analysis, we plan to run either a t test or Wilcoxon test (numerical variables) and Pearson's χ2 or Fisher's exact test (categorical data), as appropriate. DISCUSSION: Evidence suggests that the anti-inflammatory action of omega-3 PUFAs may have beneficial effects on chronic chagasic cardiomyopathy, as shown for other cardiomyopathies, due to improved control of the inflammatory response. At the end of the study, we predict that patients will have lower inflammatory markers and an improved metabolic and anthropometric profile. TRIAL REGISTRATION: Current Controlled Trials NCT01863576.

Left atrial and left ventricular diastolic function in chronic Chagas disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ± 2.8 cm/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 ± 4 mL/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. CONCLUSIONS: 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.

Predictive value of transforming growth factor-ß1in Chagas disease: towards a biomarker surrogate of clinical outcome.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) may be implicated in the development of Chagas heart disease. However, the clinical value of TGF-ß1 measurement is yet to be determined. METHODS: We retrospectively analyzed the outcome of 54 Chagas disease patients without heart failure and with left ventricular (LV) ejection fraction >45% whose TGF-ß1 serum values were determined between January 1998 and December 1999. Primary end point was all-cause mortality and secondary end point was the combination of all-cause mortality or hospitalization due to worsening heart failure or cardiac arrhythmias. RESULTS: TGF-ß1 was independently associated with the occurrence of the primary and secondary end points. The optimal cutoff for TGF-ß1 to identify the primary end point was 12.9 ng/ml (area under the curve = 0.82, p = 0.004, sensitivity 100%, and specificity 57%) and to identify the secondary end point was 30.8 ng/ml (area under the curve = 0.72, p = 0.03, sensitivity 60%, and specificity 86%). LV ejection fraction and LV end-diastolic diameter were also independent predictors of the primary and secondary endpoints, respectively. CONCLUSION: The described association between TGF-ß1 and clinical outcome provides evidence towards the clinical value of TGF-ß1 in Chagas disease.

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

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

Safety of benznidazole use in the treatment of chronic Chagas' disease.

OBJECTIVES: To assess the safety of benznidazole use in adult patients with chronic Chagas' disease. METHODS: The Naranjo algorithm was applied to classify the causality of adverse drug reactions (ADRs). RESULTS: In total, 190 patients were treated with benznidazole over a period of 4-180 days (mean 58.90 ± 36.54 days) with a dose of 50-500 mg/day (221.33 ± 57.16 mg/day). Of the 190 patients treated, 93 had ADRs and 59 of these interrupted treatment. There was a higher incidence of ADRs among female and young adult patients. There was a higher incidence of ADRs during the first 30 days of treatment. Interruption of treatment was more frequent in women. Among the patients who interrupted treatment, 39 had mild ADRs, 19 had moderate ADRs and 1 had a severe ADR. There were no interruptions in treatment for 97 patients without ADRs. The survival curves indicated that the time until interruption of treatment in patients with moderate and severe ADRs was lower than in patients with mild or no ADRs. The most frequent disorders were in the skin (26.3%), gastrointestinal system (9.5%) and nervous system (5.3%). CONCLUSIONS: The Naranjo algorithm was a useful tool to reduce the underreporting of ADRs. Events were common, but were associated with low morbidity and were reversible upon discontinuation of drug treatment. Moreover, there were no fatal events; therefore, benznidazole treatment was considered safe.

Biodistribution of bone marrow mononuclear cells in chronic chagasic cardiomyopathy after intracoronary injection.

BACKGROUND: Animal and human clinical studies have indicated that bone marrow (BM) mononuclear cell (MNC) therapy for Chagasic Cardiomyopathy (ChC) is feasible, safe and potentially efficacious. Nevertheless, little is known about the retention of these cells after intracoronary (IC) infusion. METHODS: Our study investigated the homing of technetium-99m ((99m)Tc) labeled BM MNCs and compared it to thallium-201 ((201)Tl) myocardial perfusion images using the standard 17-segment model. Six patients with congestive heart failure of chagasic etiology were included. RESULTS: Scintigraphic images revealed an uptake of 5.4%±1.7, 4.3%±1.5 and 2.3%±0.6 of the total infused radioactivity in the heart after 1, 3 and 24h, respectively. The remaining activity was distributed mainly to the liver and spleen. Of 102 segments analyzed, homing took place in 36%. Segments with perfusion had greater homing (58.6%) than those with decreased or no perfusion (6.8%), p<0.0001. There was no correlation between the number of injected cells and the number of segments with homing for each patient (r=-0.172, p=0.774). CONCLUSIONS: These results indicate that (99m)Tc-BM MNCs delivered by IC injection homed to the chagasic myocardium. However, cell biodistribution was heterogeneous and limited, being strongly associated with the myocardial perfusion pattern at rest. These initial data suggest that the IC route may present limitations in chagasic patients and that alternative routes of cell administration may be necessary.

Development and validation of a risk score for predicting death in Chagas' heart disease.

BACKGROUND: Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death in patients with Chagas' heart disease. METHODS: We retrospectively evaluated 424 outpatients from a regional Brazilian cohort. The association of potential risk factors with death was tested by Cox proportional-hazards analysis, and a risk score was created. The model was validated in 153 patients from a separate community hospital. RESULTS: During a mean follow-up of 7.9 years, 130 patients in the development cohort died. Six independent prognostic factors were identified, and each was assigned a number of points proportional to its regression coefficient: New York Heart Association class III or IV (5 points), evidence of cardiomegaly on radiography (5 points), left ventricular systolic dysfunction on echocardiography (3 points), nonsustained ventricular tachycardia on 24-hour Holter monitoring (3 points), low QRS voltage on electrocardiography (2 points), and male sex (2 points). We calculated risk scores for each patient and defined three risk groups: low risk (0 to 6 points), intermediate risk (7 to 11 points), and high risk (12 to 20 points). In the development cohort, the 10-year mortality rates for these three groups were 10 percent, 44 percent, and 84 percent, respectively. In the validation cohort, the corresponding mortality rates were 9 percent, 37 percent, and 85 percent. The C statistic for the point system was 0.84 in the development cohort and 0.81 in the validation cohort. CONCLUSIONS: A simple risk score was developed to predict death in Chagas' heart disease and was validated in an independent cohort.

T-wave axis deviation as an independent predictor of mortality in chronic Chagas' disease.

The T-wave axis shift has been reported to represent a general marker of ventricular repolarization abnormalities and a potential indicator of increased risk for cardiovascular mortality. We assessed the prognostic importance of the T-wave axis deviation for mortality rate in patients with chronic Chagas' disease. In a long-term follow-up prospective study, 738 adult outpatients in the chronic phase of Chagas' disease were enrolled. The frontal plane T-wave axis was estimated from 12-lead electrocardiograms obtained on admission and categorized as normal (15 degrees to 75 degrees ), borderline (75 degrees to 105 degrees or 15 degrees to -15 degrees ), and abnormal (>105 degrees or < -15 degrees ). Clinical and radiologic data, 2-dimensional echocardiographic data, and other electrocardiographic data were also recorded. Primary end points were all-cause, those related to Chagas' disease, and sudden cardiac deaths. Statistical analyses included Kaplan-Meier estimation of survival curves and multivariate Cox's proportional hazards models. During a follow-up of 58 +/- 39 months, 62 patients died, 54 from causes related to Chagas' disease and 40 due to sudden cardiac death. Kaplan-Meier survival curves showed that the 3 categories of T axis had significantly different prognoses. Multivariate Cox's survival analysis demonstrated that an abnormal T axis increases the risk of death threefold and sudden death nearly sixfold after adjustment for other covariates, including left ventricular systolic function and other electrocardiographic abnormalities. Borderline T-wave axis also indicated a worse prognosis, particularly in the subgroup of patients with abnormal baseline electrocardiograms. These results indicate that T-wave axis deviation is an easily quantified, strong, and independent mortality risk predictor in patients with chronic Chagas' disease.

Valor prognóstico da largura do complexo QRS na cardiopatia chagásica crônica com disfunção ventricular moderada ou grave / The prognostic value of the QRS complex length on the chronic chagasic cardiomyopathy with severe or moderate ventricular dysfunction

Objetivo: Avaliar o valor prognóstico, em relação à mortalidade cardíaca, da largura do complexo QRS (LQRS), em uma coorte de pacientes com cardiopatia chagásica crônica e disfunção ventricular moderada ou grave (DISF). Métodos: Estudo prospectivo, observacional, de coorte, constituída por 738 pacientes com diagnóstico sorológico de doença de Chagas, acompanhados no período de 03/90 a 12/99. Todos os pacientes foram submetidos a avaliação clínica, eletrocardiográfica, radiológica e ecocardiográfica. DIS foi definida por fração de ejeção ...

Electrocardiographic ventricular repolarization parameters in chronic Chagas' disease as predictors of asymptomatic left ventricular systolic dysfunction.

Electrocardiographic repolarization parameters are potential markers of arrhythmogenic risk and have not been evaluated in Chagas' disease. The aim of this report was to investigate their associations with LV systolic function assessed by two-dimensional echocardiography. In a cross-sectional study involving 738 adult outpatients in the chronic phase of Chagas' disease, maximal QTc and T wave peak-to-end (TpTe) intervals, and QT, QTapex (QTa), IT and TpTe interval dispersions, and variation coefficients were measured and calculated from 12-lead standard ECGs. Clinical, radiological, ECG, and echocardiographic data were recorded. In bivariate statistical analysis, all repolarization parameters were significantly increased in patients with moderate or severe LV systolic dysfunction, and these patients showed more clinical, radiologic, and ECG abnormalities. Receiver operating characteristic curve analysis demonstrated that isolatedly QTd had the best predictive performance for LV dysfunction, with an 80% specificity and 67% sensitivity for values >60 ms in the subgroup of chagasic patients with abnormal ECGs and no heart failure. Multivariate logistic regression selected, as the best predictive model for LV dysfunction in this subgroup of patients, the presence of cardiomegaly on chest X ray (OR 14.06, 95% CI, 5.54-35.71), QTd >60 ms (OR 9.35, 95% CI, 4.01-21.81), male gender (OR 7.70, 95% CI, 2.98-19.91) and the presence of frequent premature ventricular contractions (PVCs) on ECG (OR 4.06, 95% CI, 1.65-9.97). This model showed 90% specificity and 71% sensitivity. In conclusion, QTd was associated to LV systolic function and could be used to predict asymptomatic dysfunction in chronic Chagas' disease. The presence of cardiomegaly, frequent PVCs, and male sex refined LV function stratification in these patients.

Implication of transforming growth factor-beta1 in Chagas disease myocardiopathy.

Cardiac dysfunction with progressive fibrosis is a hallmark of Chagas disease. To evaluate the involvement of transforming growth factor (TGF)-beta1 in this disease, TGF-beta1 levels in patients were measured at 3 stages: asymptomatic indeterminate (IND), cardiac with no or slight heart dysfunction (Card 1), and cardiac with moderate or severe heart dysfunction (Card 2). All patients had significantly higher circulating levels of TGF-beta1 than did healthy persons, and 27% of patients in the Card 1 group had higher TGF-beta1 levels than did patients in the IND group. Immunohistochemical analysis of cardiac biopsy specimens showed strong fibronectin staining in the extracellular matrix and staining for phosphorylated Smad 2 (activation of the TGF-beta1 signaling pathway) in cell nuclei. The higher levels of latent TGF-beta1 observed in patients with myocardiopathy, together with intracellular activation of the TGF-beta1 pathway and tissue fibrosis, suggest that TGF-beta1 plays an important role in Chagas disease. TGF-beta1 may represent a new target for preventive and curative treatments of Chagas disease.

Progressive Chagas' cardiomyopathy is associated with low selenium levels.

Selenium (Se) deficiency is linked with some cardiomyopathies. Its status was determined in 170 patients with chronic Chagas' disease from 2 Brazilian regions (Rio de Janeiro and Belo Horizonte), clinically stratified into groups as follows: indeterminate or asymptomatic (IND); cardiac asymptomatic (CARDa); cardiac symptomatic with moderate to severe heart dysfunction (CARDb); and healthy adults (HA), used for comparison. In most HA, Se levels were normal, excluding an overall Se deficiency. Se was significantly lower in CARDb than in HA, IND, or CARDa patients. This was not associated with a concomitant decrease in activity of glutathione peroxidase. Thyrotropin was normal, excluding iodine deficiency. Se correlated positive and significantly with ventricular ejection fraction (assessed via echocardiography). Asymptomatic children with acute Chagas' disease had normal Se as well as 5 noninfectious cases of cardiomyopathy. Low Se was found in 6 of 10 chagasic patients with digestive megasyndromes. Thus, the decrease in Se in chagasic patients seems to be a biological marker for Trypanosoma cruzi infection and related to the progression of pathology.

Análise das alteraçöes cardiovasculares em adultos com deficiência de hormônio de crescimento através da Dopplerecocardiografia e do teste de esforço cardiopulmonar / Analysis of the cardiovascular changes im adults with growth hormone deficiency through of the dopplerechocardiography and of the cardiopulmonar effort test

A síndrome de deficiência de hormônio do crescimento (GHD) no adulto está bem estabelecida, assim como os benefícios da terapia com reposiçäo de hormônio de crescimento (GH). Dentre os aspectos mais estudados observam-se as alteraçöes cardiovasculares. Tem sido descrito aumento de mortalidade, maior incidência de aterosclerose e alteraçöes da funçäo cardíaca. Através da análise da funçäo cardíaca sistólica e diastólica pela dopplerecocardiografia e do comportamento no teste de esforço cardiopulmonar, foram avaliadas as alteraçöes cardiovasculares em 26 pacientes com GHD, sendo 4 com deficiência desde a infância (cGHD) e 22 com déficit adquirido na vida adulta (aGHD). Notou-se alteraçäo da funçäo cardíaca diastólica em 2 pacientes (7,7 por cento), sem alteraçöes na funçäo sistólica e em 3 pacientes observou-se reduçäo dos valores de stress sistólico do ventrículo esquerdo. Em 1 paciente havia reduçäo da massa ventricular indexada pela superfície corporal. Na análise do teste de esforço observou-se diminuiçäo da capacidade ao exercício (avaliaçäo de V02 máximo atingido) em 92 por cento dos pacientes, e resposta inotrópica reduzida representada pelo pulso de oxigênio (V02/FC) em 69 por cento dos indivíduos. Conclui-se que adultos com GHD têm capacidade funcional reduzida e disfunçäo cardíaca sistólica incipiente. A avaliaçäo em repouso pela Dopplerecocardiografia näo demonstrou alteraçöes expressivas nesta populaçäo.

Cateterismo cardíaco à beira do leito: vantagens e desvantagens / Bedside cardiac catheterization: advantages and disadvantages

Foram estudados 300 pacientes submetidos a cateterismo cardíaco direito à beira do leito (CCDBL) pela técnica de Swan-Ganz, visando avaliar a relaçäo das medidas obtidas com a classificaçäo de Killip-Kimball, e determinar a prevalência de complicaçöes. Dos 300 casos, 267 (89%) eram portadores de infarto agudo do miocárdio (IAM), estando 146 em classe II, 36 em classe III e 71 em classe IV. A introduçäo do cateter obteve êxito em 288 casos (96%), conseguindo-se obter a medida da pressäo encravada na artéria pulmonar (PEAP) em 236 (78,7%) doentes. Nos casos de IAM, a medida da PEAP estava abaixo de 18 mmHg em 47,2% dos pacientes em classe II, em 44,1% daqueles em classe III e em 35,3% dos casos em classe IV. Intercorrências ocorreram em 33 pacientes (11%): ruptura do balonete em 12 (4%), arritmias transitórias em 11 (3,7%) e obstruçäo do cateter em 10 (3,3%). Houve complicaçöes em 45 casos (14,7%): infarto pulmonar em 18 (6%), flebite em 15 (5%), arritmia persistente em 10 (3,3%), ruptura da artéria pulmonar e endocardite infecciosa em um caso cada. As médias de idade foram semelhantes nos grupos com e esem complicaçöes, mas o tempo de permanência do cateter foi significativamente maior no grupo com complicaçöes: 3,4 ñ 0,2 vs 2,7 ñ 0,1 dias (p < 0,05). Concluímos que percentagem apreciável de pacientes clinicamente em classes II, III e IV apresentavam PEAP abaixo de 18 mmHg. O tempo de permanência do cateter constituiu-se num importante fator de desencadeamento de complicaçöes...