The Selvester QRS score as an estimative of myocardial injury in acute chagasic patients from the Brazilian Amazon.

BACKGROUND: In the Brazilian Amazon, a new epidemiological profile of Chagas disease transmission, the oral route, has been detected and cited as being responsible for the increase in acute cases in Brazil. The clinical evaluation of acute Chagas disease (ACD) has been a challenge since it can progress to a chronic phase with cardiac alterations, and the follow-up by modern diagnostic methods is very difficult due to the socio-geographical characteristics of the Brazilian Amazon. Thus, alternatives should be sought to alleviate this problem. We conducted a study to evaluate subjects with ACD using the 12-lead ECG QRS score (Selvester score) as an estimative of myocardial injury progression before and after ACD treatment. METHODS: The study included indigenous subjects from the Amazon region with ACD in clinical follow-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) Chagas Disease outpatient clinic in the state of Amazonas, Brazil. The control group consisted of 31 healthy volunteers with no history of heart disease and no reactive serology for Chagas disease. Baseline ECG was performed in all subjects. The Selvester scoring method was performed according to the standardized guide (< 3 points: no myocardial injury,> 3: points × 3% = % of the predicted LV infarction). RESULTS: A total of 62 subjects were included, 31 as cases and 31 as controls. The mean follow-up of the case group was 17 months. The control group presented normal ECG. The case group presented 13 alterations before treatment and 11 after. Nineteen individuals presented scores > 3 points, 6 before and 13 after. In 19.36% of subjects, myocardial injury was found before treatment and in 41.94% after treatment. CONCLUSION: This is the first study that uses the Selvester score (SS) to predict myocardial injury in subjects with ACD. The results of this study suggest the significant presence of myocardial injury from the beginning of treatment to the period post treatment of ACD, which demonstrates that the SS can be applied for stratification and follow-up of Chagas disease in the Amazon region.

Noninvasive prediction of late potentials in the signal-averaged ECG in patients with chronic Chagas disease.

INTRODUCTION: Considering the importance of ventricular arrhythmias in the prediction of sudden cardiac death in chronic Chagas heart disease, the aim of the present study was to associate late potentials observed in the signal-averaged electrocardiogram (SAECG) with either non-sustained ventricular tachycardia in the 24-hour Holter monitoring or reduced left ventricular ejection fraction in the 2-dimension echocardiogram. METHODS: This was a retrospective transversal study. The medical charts of 49 patients with chronic Chagas heart disease that underwent 24-hour Holter monitoring at our institution from September 2012 to December 2015 were reviewed. In the univariate analysis, variables associated with SAECG at a p value <0.05 were entered a multivariate stepwise logistic regression analysis through the model forward. A p value <0.05 was considered to have statistical significance. RESULTS: In the univariate analysis, right bundle branch block, left atrial diameter, left ventricular systolic diameter, and left ventricular ejection fraction were associated with late potential in the SAECG. In the multivariate analysis, however, right bundle branch block and left atrial diameter were retained as independent predictors of late potentials in the SAECG. CONCLUSIONS: Neither ventricular arrhythmias in the 24-Holter monitoring nor reduced left ventricular ejection fraction in the 2-D echocardiogram were associated with late potentials in the SAECG of patients with chronic Chagas heart disease.

Human platelet antigen polymorphisms and the risk of chronic Chagas disease cardiomyopathy.

Human platelet antigen (HPA) polymorphisms are considered to be a risk factor for cardiac and vascular diseases, but the role of HPA in chronic Chagas disease cardiomyopathy (CCC) is not available. Therefore, the aim of this study was to investigate the association of HPA polymorphisms, HPA-1, HPA-2, HPA-3, HPA-5 and HPA-15, in the severity of left ventricular systolic dysfunction (LVSD) in CCC patients. For this, 229 CCC patients were separated into three groups: without LVSD, mild/moderate LVSD and severe LVSD. PCR-SSP was performed for HPA genotyping and the risk was assessed using SNPStats software. HPA-1 allele and genotype frequencies were lower in mild/moderate LVSD patients compared to other groups, without statistical significance. After stratified analyzes, the HPA-3a/3b genotype frequency was lower in women with severe LVSD compared to those without LVSD (OR:0.29; 95% CI: 0.10-0.84). In conclusion, HPA-3 variant could be a protection factor for CCC in the female patients.

Students' perception of animal or virtual laboratory in physiology practical classes in PBL medical hybrid curriculum.

Over the years, much criticism against animal use for physiology teaching has been made. Hence, replacement by suitable alternatives has increased in several pedagogical approaches. This study examined students' perceptions of animal versus virtual (video/computer) laboratory classes in physiological sciences associated with the effectiveness of the problem-based learning (PBL) hybrid curriculum. Three cohorts of medical students from the University of Ribeirão Preto, who participated in animal or virtual physiology classes or both, were asked to fill out a 5-point Likert questionnaire about knowledge acquisition/motivation, importance to PBL learning goals, skills acquired, need for animal use, academic formation, learning impairment, and alternative methods. We also assessed their grades in the final exam. A total of 350 students were included, in which 108 participated only in virtual classes, 120 only in practical animal laboratory classes, and 122 in both approaches. The majority agreed that the two methods improved their knowledge acquisition/motivation and helped to reinforce tutorial goals and to acquire skills. However, the cohort who experienced both approaches favored animal laboratory. Students believe animal use is needed and did not impair their learning. Conversely, their opinion about academic formation without animal laboratory classes was divided, as was whether this approach inspired them to seek alternative methods. Despite the different perceptions, there was no difference among the groups' final grades (7.3 ± 1 vs. 7.2 ± 1 vs. 7.2 ± 2 for virtual or practical animal laboratory classes or both, respectively). Therefore, virtual activities are not as effective as animal use in the opinions of the students, but they are successful strategies in physiology learning that can be used in practical classes in a hybrid PBL curriculum.

Curcumin Analog CH-5 Suppresses the Proliferation, Migration, and Invasion of the Human Gastric Cancer Cell Line HGC-27.

Gastric cancer is one of the most frequent malignant tumors in the world. The majority of patients are diagnosed with metastatic gastric cancer, which has a low survival rate. These data reinforce the importance of studying the anticancer activity of new molecules with the potential to suppress gastric cancer metastasis. Curcumin is a well-studied compound that has demonstrated anti-metastatic effects. Here we investigated if CH-5, a curcumin derivative compound, has anti-metastatic properties in the human gastric cancer cell line HGC-27. Firstly, we found that CH-5 decreased viability and induced apoptosis in HGC-27 cells in a dose-dependent manner. Additionally, CH-5 suppressed the migration and invasion of HGC-27 cells by downregulating the expression and collagenase activity of matrix metalloproteinase 2 in a dose-dependent manner. In conclusion, CH-5 showed anticancer activities, including the induction of apoptosis, and the suppression of migration and invasion in HGC-27 cells, suggesting that CH-5 can be a lead molecule for the development of anti-metastatic drugs for gastric cancer therapy.

Plasma concentrations of CCL3 and CCL4 in the cardiac and digestive clinical forms of chronic Chagas disease.

The aim of this study was to investigate the plasma levels of the CCL3 and CCL4 chemokines in patients with the cardiac and digestive clinical forms of chronic Chagas disease and in cardiac patients with and without left ventricular systolic dysfunction (LVSD). Plasma samples from 75 patients were evaluated by enzyme-linked immunosorbent assay (ELISA) to confirm infection by T. cruzi. Plasma levels of the CCL3 and CCL4 chemokines were measured using Milliplex® MAP assay (Millipore). There were no significant differences in the levels of CCL3 and CCL4 between patients with the digestive and cardiac clinical forms of Chagas disease. Moreover, no significant differences were found between patients without LVSD and those with LVSD. Higher CCL3 and CCL4 plasma levels were found in patients with LVSD compared to those with the digestive form of the disease. The CCL3 and CCL4 chemokines might not be involved in differential susceptibility to the digestive and cardiac clinical forms of chronic Chagas disease, and it seems they do not influence the development of LVSD.

Association of the Functional MICA-129 Polymorphism With the Severity of Chronic Chagas Heart Disease.

MICA-129 polymorphism affects the binding affinity of MICA molecules with the NKG2D receptor and influences effector cell function. The genotype met/met was associated with the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease, while the val/val genotype was associated with the absence of LVSD.

A Comparison of the Academic Achievement at the End of the Medicine Undergraduate Degree Program Between Students Who Only Used the University Admission Test and Those Who Used the University Admission Test Plus Marks from the High School National Exam (ENEM) at a Single Brazilian Center.

Purpose: The role of marks in the University Admission Test (UAT) plus the marks from pre-university academic records in predicting academic achievement at the end of the Medicine undergraduate degree program is not completely known. This study was undertaken to compare the performance of marks in the UAT alone with those of the UAT plus marks from the National High School Exam (ENEM in Brazil) regarding students' outcomes at the end of the Medicine undergraduate degree program. Methods: Fifty-one (51) students from the last semester (12th) of our Medicine undergraduate degree program were included in the study. They were divided into a group of those who used the marks obtained in the UAT plus the marks obtained in the ENEM (ENEM group, n=9), and those who only used the marks in the UAT (non-ENEM group, n=42). We compared the academic achievement of the non-ENEM group with that of the ENEM group regarding the mean marks obtained in the clerkship, in the Progress Test (PT), and in the Objective Structured Clinical Examination (OSCE). Results: The mean scores obtained in the disciplines of the clerkship were higher in the non-ENEM group compared to the ENEM group (7.32 ± 0.41 vs 6.98 ± 0.31, p= 0.01). Both groups obtained similar mean marks in the OSCE and in the PT. A moderate correlation was observed between the marks in the clerkship with those of the UAT from the non-ENEM group (p=0.00006; r=0.45). Conclusion: Marks of the UAT alone appear to be associated with a higher academic achievement in the clerkship than marks of the UAT plus scores obtained from the ENEM at the end of the Medicine undergraduate degree program.

Does left ventricular reverse remodeling influence long-term outcomes in patients with Chagas cardiomyopathy?

BACKGROUND: The impact of left ventricular reverse remodeling (LVRR) on the prognosis of Chagas cardiomyopathy is unknown. The aim of this study was to determine whether the presence of LVRR can predict mortality in these patients. METHODS: From January 2000 to December 2010, the medical charts of 159 patients were reviewed. LVRR was defined as an increase of left ventricular ejection fraction (LVEF) and a decrease of left ventricular end-diastolic diameter (LVDD) by two-dimensional echocardiography. No patient underwent cardiac resynchronization therapy or required mechanical ventricular assistance. RESULTS: At baseline, median (25th-75th) LVDD was 64 mm (59-70), and median LVEF was 33.2% (26.4-40.1). LVRR was detected in 24.5% of patients in a 40-month (26-64) median follow-up. In the LVRR group, LVDD decreased from 64 mm (59-68) to 60 mm (56-65; p < 0.001), and LVEF increased from 31.3% (24.1-39.0) to 42.5% (32.2-47.7; p < 0.001). However, LVRR was not associated with heart failure hospitalization, cardiogenic shock, heart transplantation, or mortality (p > 0.05 for all comparisons). The Cox proportional hazard model analysis identified only cardiogenic shock (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 1.51-3.85; p < 0.001) and serum sodium level (HR: 0.91; 95% CI: 0.86-0.96; p < 0.001) as independent predictors of all-cause mortality. CONCLUSIONS: Left ventricular reverse remodeling occurs in one quarter of patients with Chagas cardiomyopathy and have no impact on the outcomes of patients with this condition.

Management of Cardiovascular Disease in Patients With COVID-19 and Chronic Chagas Disease: Implications to Prevent a Scourge Still Larger.

Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in the general population. Because the high prevalence of COVID-19 and chronic Chagas disease (CCD) where the latter is endemic, all such diseases will likely be observed in the same patient. While COVID-19 can provoke generalized endotheliitis, which can lead to a cytokine storm and a hyper-coagulable state culminating into in-site and at a distance thrombosis. Therefore, small-vessel coronary artery disease (CAD), cerebrovascular disease, thromboembolism, and arrhythmias are prominent findings in COVID-19. In CCD, small-vessel CAD, cardioembolic stroke, pulmonary embolism, heart failure and arrhythmias are frequently observed as a result of a similar but less intense mechanism. Consequently, the association of CCD and COVID-19 will likely increase the incidence of CVD. Thus, doctors on the frontline should be on the alert for this diagnostic possibility so that the proper treatment can be given without any delay.

MICA and KIR: Immunogenetic Factors Influencing Left Ventricular Systolic Dysfunction and Digestive Clinical Form of Chronic Chagas Disease.

Tissue damage observed in the clinical forms of chronic symptomatic Chagas disease seems to have a close relationship with the intensity of the inflammatory process. The objective of this study was to investigate whether the MICA (MHC class I-related chain A) and KIR (killer cell immunoglobulin-like receptors) polymorphisms are associated with the cardiac and digestive clinical forms of chronic Chagas disease. Possible influence of these genes polymorphisms on the left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease was also evaluated. This study enrolled 185 patients with positive serology for Trypanosoma cruzi classified according to the clinical form of the disease: cardiac (n=107) and digestive (n=78). Subsequently, patients with the cardiac form of the disease were sub-classified as with LVSD (n=52) and without LVSD (n=55). A control group was formed of 110 healthy individuals. Genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). Statistical analyzes were carried out using the Chi-square test and odds ratio with 95% confidence interval was also calculated to evaluate the risk association. MICA-129 allele with high affinity for the NKG2D receptor was associated to the LVSD in patients with CCHD. The haplotype MICA*008~HLA-C*06 and the KIR2DS2-/KIR2DL2-/KIR2DL3+/C1+ combination were associated to the digestive clinical form of the disease. Our data showed that the MICA and KIR polymorphisms may exert a role in the LVSD of cardiac patients, and in digestive form of Chagas disease.

The use of the CALL Risk Score for predicting mortality in Brazilian heart failure patients.

AIMS: This study aimed to develop and validate a simple method for predicting long-term all-cause mortality in ambulatory patients with chronic heart failure (CHF) residing in an area where Chagas disease is endemic, which will be important not only for patients living in Latin America but also to those living in developed non-endemic countries. METHODS AND RESULTS: A total of 677 patients with a wide spectrum of aetiologies for left ventricular systolic dysfunction and receiving optimized evidence-based treatment for CHF were prospectively followed for approximately 11 years. We established a risk score using Cox proportional hazard regression models. After multivariable analysis, four variables were independently associated with mortality and included in the CALL Risk Score: Chagas cardiomyopathy aetiology alone [hazard ratio, 3.36; 95% confidence interval (CI), 2.61-4.33; P < 0.001], age ≥60 years (hazard ratio, 1.36; 95% CI, 1.06-1.74; P = 0.016), left anterior fascicular block (hazard ratio, 1.64; 95% CI, 1.27-2.11; P < 0.001), and left ventricular ejection fraction <40% (hazard ratio, 1.73; 95% CI, 1.30-2.28; P < 0.001). The internal validation considered the bootstrapping, a resampling technique recommended for prediction model development. Hence, we established a scoring system attributing weights according to each risk factor: 3 points for Chagas cardiomyopathy alone, 1 point for age ≥60 years, and 2 points each for left anterior fascicular block and left ventricular ejection fraction <40%. Three risk groups were identified: low risk (score ≤2 points), intermediate risk (score of 3 to 5 points), and high risk (score ≥6 points). High-risk patients had more than two-fold increase in mortality (26.9 events/100 patient-years) compared with intermediate-risk patients (10.1 events/100 patient-years) and almost seven-fold increase compared with low-risk patients (4.3 events/100 patient-years). The CALL Risk Score data sets from the development and internal validation cohorts both displayed suitable discrimination c-index of 0.689 (95% CI, 0.688-0.690; P < 0.001) and 0.687 (95% CI, 0.686-0.688; P < 0.001), respectively, and satisfactory calibration [Greenwood-Nam-D'Agostino test (8) = 7.867; P = 0.447] and [Greenwood-Nam-D'Agostino test (8) = 10.08; P = 0.273], respectively. CONCLUSIONS: The CALL Risk Score represents a simple and validated method with a limited number of non-invasive variables that successfully predicts long-term all-cause mortality in a real-world cohort of patients with CHF. Patients with CHF stratified as high risk according to the CALL Risk Score should be monitored and aggressively managed, including those with CHF secondary to Chagas disease.

Prognostic Significance of Chronic Kidney Disease (CKD-EPI Equation) and Anemia in Patients with Chronic Heart Failure Secondary to Chagas Cardiomyopathy.

BACKGROUND: Few studies regarding chronic kidney disease (CKD) and anemia have been conducted in patients with Chagas cardiomyopathy (CC). We evaluated the risk prediction performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and anemia in CC patients. METHODS: From 2000 to 2010, a total of 232 patients were studied in a single-center retrospective study. CKD was defined as creatinine clearance <60 mL/min/1.73 m2 according to CKD-EPI equation. Anemia was defined as hemoglobin <12 g/dL (women) and <13 g/dL (men). Cox proportional hazards models were used to establish predictors for death. RESULTS: At baseline, 98 individuals (42.2%) had criteria for CKD and 41 (17.7%) for anemia. During follow-up, 136 patients (58.6%) died. Independently, CKD and anemia were not associated with all-cause mortality. However, when they coexisted, an additional risk was attributed for these patients. Cox proportional hazard models analysis identified systolic blood pressure (hazard ratio, 0.99; 95% confidence interval (CI), 0.98 to 1.00; P=0.015), implantable cardioverter-defibrillator (hazard ratio, 0.48; 95% CI, 0.27 to 0.85; P=0.012), left anterior fascicular block (hazard ratio, 1.52; 95% CI, 1.08 to 2.13; P=0.017), left ventricular end-diastolic diameter (hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P < 0.001), and serum sodium (hazard ratio, 0.95; 95% CI, 0.92 to 0.99; P=0.020) as independent predictors for death. CONCLUSIONS: CKD and anemia are not independent predictors for long-term mortality in CC patients. However, the prognosis is poorer in individuals with both comorbidities.

Abnormalities in electrocardiographic ventricular repolarization in patients with dengue virus infection.

INTRODUCTION: Dengue virus infection (DENV) is an arboviral disease that affects millions of people in many countries throughout the world every year. The disease is caused by the bite of a mosquito (Aedes aegypti and / or Aedes albopictus). The symptoms/signs observed in this arboviral disease are unspecific, and the blood count usually shows leukopenia and thrombocytopenia. Although ECG changes may be observed in DENV, little is known about parameters of ventricular repolarization in patients with this condition. Accordingly, the aim of this study was to evaluate the QTc and QT interval dispersion to detect ventricular repolarization changes in patients with DENV. METHODOLOGY: Ninety-three consecutive patients seen during DENV epidemics in a small town with non-complicated DENV were included; 93 normal individuals served as controls. Clinical data, blood count and the 12-lead ECG were obtained from each individual. RESULTS: The QTc duration was higher in patients with DENV in comparison to controls. Furthermore, 5% of DENV patients had abnormal lengthening of the QTc interval. No difference regarding QT interval dispersion was observed between DENV patients and controls. No DENV patient had increased lengthening of the QT interval dispersion. CONCLUSIONS: Myocardial repolarization changes do occur in patients with DENV. Having into account the potential impact of these changes on patients' outcome, and because 12-lead ECG is not routinely recommended in the setting of DENV in our country, we recommend that a 12-lead ECG be taken from each patient with this condition during DENV epidemics.

Chronic Chagas Heart Disease Management: From Etiology to Cardiomyopathy Treatment.

Trypanosoma cruzi (T. cruzi) infection is endemic in Latin America and is becoming a worldwide health burden. It may lead to heterogeneous phenotypes. Early diagnosis of T. cruzi infection is crucial. Several biomarkers have been reported in Chagas heart disease (ChHD), but most are nonspecific for T. cruzi infection. Prognosis of ChHD patients is worse compared with other etiologies, with sudden cardiac death as an important mode of death. Most ChHD patients display diffuse myocarditis with fibrosis and hypertrophy. The remodeling process seems to be associated with etiopathogenic mechanisms and neurohormonal activation. Pharmacological treatment and antiarrhythmic therapy for ChHD is mostly based on results for other etiologies. Heart transplantation is an established, valuable therapeutic option in refractory ChHD. Implantable cardioverter-defibrillators are indicated for prevention of secondary sudden cardiac death. Specific etiological treatments should be revisited and reserved for select patients. Understanding and management of ChHD need improvement, including development of randomized trials.

Genetic Polymorphisms of IL17 and Chagas Disease in the South and Southeast of Brazil.

The aim of this study was to investigate possible associations between genetic polymorphisms of IL17A G197A (rs2275913) and IL17F T7488C (rs763780) with Chagas Disease (CD) and/or the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas cardiomyopathy (CCC). The study with 260 patients and 150 controls was conducted in the South and Southeast regions of Brazil. The genotyping was performed by PCR-RFLP. The A allele and A/A genotype of IL17A were significantly increased in patients and their subgroups (patients with CCC; patients with CCC and LVSD; and patients with CCC and severe LVSD) when compared to the control group. The analysis according to the gender showed that the A/A genotype of IL17A was more frequent in female with LVSD and mild to moderate LVSD and also in male patients with LVSD. The frequency of IL17F T/C genotype was higher in male patients with CCC and severe LVSD and in female with mild to moderate LVSD. The results suggest the possible involvement of the polymorphisms of IL17A and IL17F in the susceptibility to chronic Chagas disease and in development and progression of cardiomyopathy.

ABO, Secretor and Lewis histo-blood group systems influence the digestive form of Chagas disease.

Chagas disease, caused by Trypanosoma cruzi, can affect the heart, esophagus and colon. The reasons that some patients develop different clinical forms or remain asymptomatic are unclear. It is believed that tissue immunogenetic markers influence the tropism of T. cruzi for different organs. ABO, Secretor and Lewis histo-blood group systems express a variety of tissue carbohydrate antigens that influence the susceptibility or resistance to diseases. This study aimed to examine the association of ABO, secretor and Lewis histo-blood systems with the clinical forms of Chagas disease. We enrolled 339 consecutive adult patients with chronic Chagas disease regardless of gender (cardiomyopathy: n=154; megaesophagus: n=119; megacolon: n=66). The control group was composed by 488 healthy blood donors. IgG anti-T. cruzi antibodies were detected by ELISA. ABO and Lewis phenotypes were defined by standard hemagglutination tests. Secretor (FUT2) and Lewis (FUT3) genotypes, determined by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), were used to infer the correct histo-blood group antigens expressed in the gastrointestinal tract. The proportions between groups were compared using the χ2 test with Yates correction and Fisher's exact test and the Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated. An alpha error of 5% was considered significant with p-values <0.05 being corrected for multiple comparisons (pc). No statistically significant differences were found for the ABO (X2: 2.635; p-value=0.451), Secretor (X2: 0.056; p-value=0.812) or Lewis (X2: 2.092; p-value=0.351) histo-blood group phenotypes between patients and controls. However, B plus AB Secretor phenotypes were prevalent in pooled data from megaesophagus and megacolon patients (OR: 5.381; 95% CI: 1.230-23.529; p-value=0.011; pc=0.022) in comparison to A plus O Secretor phenotypes. The tissue antigen variability resulting from the combined action of ABO and Secretor histo-blood systems is associated with the digestive forms of Chagas disease.