Morphologic and morphometric evaluation of pancreatic islets in chronic Chagas' disease

PURPOSE: Hyperglycemia and abnormal glucose tolerance tests observed in some patients with chronic Chagas' disease suggest the possibility of morphological changes in pancreatic islets and/or denervation. The purpose of this study was to describe the morphology and morphometry of pancreatic islets in chronic Chagas' disease. METHODS: Morphologic and computerized morphometric studies were performed in fragments of the head, body, and tail regions of the pancreas obtained at necropsies of 8 normal controls and 17 patients with chronic Chagas' disease: 8 with the digestive form (Megas) and 9 with the congestive heart failure form. RESULTS: The Megas group had a larger (p < 0.05) pancreatic islet area in the tail of the pancreas (10649.3 ± 4408.8 µm²) than the normal control (9481.8 ± 3242.4 µm²) and congestive heart failure (9475.1 ± 2104.9 µm²) groups; likewise, the density of the pancreatic islets (PI) was greater (1.2 ± 0.7 vs. 0.9 ± 0.6 vs. 1.9 ± 1.0 PI/mm², respectively). In the tail region of the pancreas of patients with the Megas form, there was a significant and positive correlation (r = +0.73) between the area and density of pancreatic islets. Discrete fibrosis and leukocytic infiltrates were found in pancreatic ganglia and pancreatic islets of the patients with Chagas' disease. Trypanosoma cruzi nests were not observed in the examined sections. Individuals with the Megas form of Chagas' disease showed increased area and density of pancreatic islets in the tail of the pancreas. CONCLUSION: The observed morphometric and morphologic alterations are consistent with functional changes in the pancreas, including glycemia and insulin disturbances.

Pancreatic lesions in acute experimental Chagas' disease

BACKGROUND: Chagas' disease is an endemic tropical affliction found from southern United States to Argentina. The acute phase of this disease is difficult to study in man because the symptoms are non-specific and most cases require no medical assistance. Experimental models have been developed for sequential studies, and intense parasitism in all organs and tissues, including the pancreas, have been detected in the acute phase. PURPOSE: To evaluate the involvement of the pancreas in acute experimental Chagas' disease in a mouse model by histopathological characterization. CASUISTIC AND METHODS: Ten BALBc mice, about 20 g, injected i.p. with 100 000 forms of the Y strain of Trypanosoma cruzi were used. The animals were sacrificed after 14 days of infection. Fragments of pancreas were processed by conventional paraffin embedding and hematoxylin-eosin staining. RESULTS: Ruptured pseudocysts and release of parasites to the extracellular medium caused by necrosis of acinar and duct cells and foci of fat were the most striking histopathological features of acute Chagasic pancreatitis. CONCLUSION: Parasitism is the main cause of acute pancreatitis in Chagas' disease.

Histoplasmosis as a late infectious complication following heart transplantation in a patient with Chagas' disease

Infectious complications following heart transplantation are an important cause of morbidity and mortality. Generally, bacterial infections are predominant; however, fungal infections can be responsible for up to 25% of infectious events. We report the case of a patient who presented with histoplasmosis as an infectious complication five years after heart transplantation due to a chagasic cardiopathy. This association has rarely been reported in the international literature.

Prevalence of Chagas' Disease in Mulungu do Morro Northeastern Brazil

OBJECTIVE - The aim of this paper is to describe the prevalence of T. Cruzi infection in patients of from Mulungu do Morro, a rural tropical region of Northeastern Brazil. METHODS - A cross-sectional study was performed. After randomly selecting samples of the population, and obtaining their consents , patients completed pretested epidemiological and clinical questionnaires. Serum samples from all patients were collected and screened for the presence of T. cruzi antibodies. RESULTS - Of 694 patients examined, 174 patients (25.1%) tested had a positive serology for Chagas' disease. Of the study population, 341 patients were male with 27% Chagas' disease prevalence, without a statistical difference. Illiteracy was the only variable related to T. cruzi infection in our population. CONCLUSION - In conclusion, our study points to the high prevalence of Chagas' disease among patients in Mulungu do Morro, suggesting that this region has a high frequency of infection and probably active vectorial transmission.

Prevalence of Cardiac Arrhythmias During and After Pregnancy in Women with Chagas' Disease without Apparent Heart Disease

OBJECTIVE: To evaluate cardiac arrhythmias during and after pregnancy in women with Chagas' disease without apparent heart disease using dynamic electrocardiography. METHODS: Twenty pregnant women with Chagas' disease without apparent heart disease aged 19 to 42 years (26.96 ± 3.6) and a control group of 20 non-chagasic pregnant patients aged 16 to 34 years (22.5 ± 4.8). The patients were submitted to passive hemagglutination and indirect immunofluorescence for the detection of Trypanosoma cruzi evaluation, and electrocardiography, echocardiography and 24-h dynamic electrocardiography. RESULTS: Supraventricular premature depolarizations were observed in 18 (90%) patients and ventricular premature depolarization in 11 (55%) patients of both groups during pregnancy. After delivery, supraventricular premature depolarizations were present in 13 (60%) chagasic patients and in 16 (89.4%) control patients (P<=0.05). Ventricular premature depolarization were observed in 9 (45%) chagasic patients and 11 (57.8%) control patients. CONCLUSION: The prevalence of ventricular premature depolarization was similar for the chagasic and control groups during and after pregnancy. The incidence of supraventricular premature depolarizations was similar in the two groups during pregnancy, while after delivery a predominance was observed in the control group compared to the chagasic group.

Doppler tissue imaging to assess systolic function in Chagas' disease

OBJECTIVE: To assess the usefulness of Doppler tissue imaging (DTI) for evaluating the systolic function of chagasic patients with and without electrocardiographic abnormalities, in comparision with echocardiographic study. METHODS: We studied 77 patients divided into 3 groups as follows: group 1 - control; group 2 - chagasic patients with normal electrocardiographic findings; and group 3 - chagasic patients with abnormal electrocardiographic findings. The following parameters were assessed: left ventricular dimensions and ejection fraction, left atrial dimensions and diastolic function on echocardiography. Systolic velocity and regional isovolumic contraction time (IVCTr) of the septal, anterior, lateral, posterior and inferior left ventricular walls were assessed on DTI. RESULTS: Left ventricular cavitary dimensions, ejection fraction and DTI systolic wave showed significant differences between groups 1 and 3 and between groups 2 and 3, which were not found between groups 1 and 2. IVCTr allowed a statistically significant discrimination among the 3 groups. CONCLUSION: DTI allowed discrimination among the different groups assessed, being superior to echocardiography in identifying early abnormalities of contractility, and, therefore, potentially useful for detecting incipient myocardial alterations in chagasic patients with normal electrocardiographic findings.

Value of the radiological study of the thorax for diagnosing left ventricular dysfunction in Chagas' disease

OBJECTIVE: To determine the value of the radiological study of the thorax for diagnosing left ventricular dilation and left ventricular systolic dysfunction in patients with Chagas' disease. METHODS: A cross-sectional study of 166 consecutive patients with Chagas' disease and no other associated diseases. The patients underwent cardiac assessment with chest radiography and Doppler echocardiography. Sensitivity, specificity, and positive and negative predictive values of chest radiography were calculated to detect left ventricular dysfunction and the accuracy of the cardiothoracic ratio in the diagnosis of left ventricular dysfunction with the area below the ROC curve. The cardiothoracic ratio was correlated with the left ventricular ejection fraction and the left ventricular diastolic diameter. RESULTS: The abnormal chest radiogram had a sensitivity of 50%, specificity of 80.5%, and positive and negative predictive values of 51.2% and 79.8%, respectively, in the diagnosis of left ventricular dysfunction. The cardiothoracic ratio showed a weak correlation with left ventricular ejection fraction (r=-0.23) and left ventricular diastolic diameter (r=0.30). The area calculated under the ROC curve was 0.734. CONCLUSION: The radiological study of the thorax is not an accurate indicator of left ventricular dysfunction; its use as a screening method to initially approach the patient with Chagas' disease should be reevaluated.

Frequency of hypertension in chronic Chagas' disease: retrospective clinical study

OBJECTIVE: To assess the frequency of hypertension in chagasic patients, as well as its clinical behavior and cardiologic findings. METHODS: We carried out a retrospective study with 225 patients with chronic Chagas' disease and hypertension (104 males), mean age of 55.1 ± 11.8. These patients were being followed up in the outpatient care clinics from 1984 to 2000. The study assessed the clinical, electrocardiographic, and radiological viewpoints. RESULTS: Of the 225 hypertensive patients (prevalence = 33.3%), 78 (34.7%) had mild hypertension, 108 (48%) had moderate hypertension, and 39 (17.3%) had severe hypertension. The association of left anterosuperior divisional block and right bundle-branch block occurred in 39 cases (17.3%), and enlargement of the cardiac area on radiological examination occurred in 93 (44.9%) of the 207 cases studied. The undetermined form of Chagas' disease was the most prevalent, 30.2% of the cases, followed by the form associated with conduction disorders in 27.1%, and the isolated form of conduction disorders in 21.3%. CONCLUSION: Chagasic patients had a frequency of hypertension similar to that of the general population, and the clinical profile of the hypertensive chagasic patients seemed not to differ a lot from that of the chagasic patients.

Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

Background:Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence.Objective:To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias.Method:Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram).Results:GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028).Conclusion:The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.

Value of the Qrs-T Angle in Predicting the Induction of Ventricular Tachyarrhythmias in Patients with Chagas Disease

Background:The QRS-T angle correlates with prognosis in patients with heart failure and coronary artery disease, reflected by an increase in mortality proportional to an increase in the difference between the axes of the QRS complex and T wave in the frontal plane. The value of this correlation in patients with Chagas heart disease is currently unknown.Objective:Determine the correlation of the QRS-T angle and the risk of induction of ventricular tachycardia / ventricular fibrillation (VT / VF) during electrophysiological study (EPS) in patients with Chagas disease.Methods:Case-control study at a tertiary center. Patients without induction of VT / VF on EPS were used as controls. The QRS-T angle was categorized as normal (0-105º), borderline (105-135º) or abnormal (135-180º). Differences between groups for continuous variables were analyzed with the t test or Mann-Whitney test, and for categorical variables with Fisher's exact test. P values < 0.05 were considered significant.Results:Of 116 patients undergoing EPS, 37.9% were excluded due to incomplete information / inactive records or due to the impossibility to correctly calculate the QRS-T angle (presence of left bundle branch block and atrial fibrillation). Of 72 patients included in the study, 31 induced VT / VF on EPS. Of these, the QRS-T angle was normal in 41.9%, borderline in 12.9% and abnormal in 45.2%. Among patients without induction of VT / VF on EPS, the QRS-T angle was normal in 63.4%, borderline in 14.6% and abnormal in 17.1% (p = 0.04). When compared with patients with normal QRS-T angle, those with abnormal angle had a fourfold higher risk of inducing ventricular tachycardia / ventricular fibrillation on EPS [odds ratio (OR) 4; confidence interval (CI) 1.298-12.325; p = 0.028]. After adjustment for other variables such as age, ejection fraction (EF) and QRS size, there was a trend for the abnormal QRS-T angle to identify patients with increased risk of inducing VT / VF during EPS (OR 3.95; CI 0.99-15.82; p = 0.052). The EF also emerged as a predictor of induction of VT / VF: for each point increase in EF, there was a 4% reduction in the rate of sustained ventricular arrhythmia on EPS.Conclusions:Changes in the QRS-T angle and decreases in EF were associated with an increased risk of induction of VT / VF on EPS.

Right Ventricular Doppler Echocardiographic Study of Indeterminate Form of Chagas Disease

Background: Patients with indeterminate form of Chagas disease/cardiac normality (ICD/CN) exhibited normal electrocardiograms and chest X-rays; however, more sophisticated tests detected some degree of morphological and functional changes in the heart. Objective: To assess the prevalence of systolic and diastolic dysfunction of the right ventricle (RV) in patients with ICD/CN. Methods: This was a case–control and prevalence study. Using Doppler two-dimensional echocardiography (2D), 92 patients were assessed and divided into two groups: group I (normal, n = 31) and group II (ICD/CN, n = 61). Results: The prevalence of RV systolic dysfunction in patients in groups I and II was as follows: fractional area change (0.0% versus 0.6%), mobility of the tricuspid annulus (0.0% versus 0.0%), and S-wave tissue Doppler (6.4% versus 26.0%, p = 0.016). The prevalence of global disorders such as the right myocardial performance index using tissue Doppler (16.1% versus 27.8%, p = 0.099) and pulsed Doppler (61.3% versus 68%, p = 0.141) and diastolic disorders such as abnormal relaxation (0.0% versus 6.0%), pseudonormal pattern (0.0% versus 0.0%), and restrictive pattern (0.0% versus 0.0%) was not statistically different between groups. Conclusion: The prevalence of RV systolic dysfunction was estimated to be 26% (S wave velocity compared with other variables), suggesting incipient changes in RV systolic function in the ICD/CN group.

Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease

Background:In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation.Objective:This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects.Methods:Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05).Results:Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDCsignificantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not.Conclusion:HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence.

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

AbstractBackground:Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated.Objective:The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.Methods:Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.Results:For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease.Conclusion:Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0)