Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels.

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.

Clinical predictors of a positive genetic test in hypertrophic cardiomyopathy in the Brazilian population.

BACKGROUND: Hypertrophic cardiomyopathy is a genetic autosomal dominant disease characterized by left ventricular hypertrophy. The molecular diagnosis is important but still expensive. This work aimed to find clinical predictors of a positive genetic test in a Brazilian tertiary centre cohort of index cases with HCM. METHODS: In the study were included patients with HCM clinical diagnosis. For genotype x phenotype comparison we have evaluated echocardiographic, electrocardiographic, and nuclear magnetic resonance measures. All patients answered a questionnaire about familial history of HCM and/or sudden death. ß-myosin heavy chain, myosin binding protein C, and troponin T genes were sequenced for genetic diagnosis. RESULTS: The variables related to a higher probability of a positive genetic test were familial history of HCM, higher mean heart frequency, presence of NSVT and lower age. Probabilities of having a positive molecular genetic test were calculated from the final multivariate logistic regression model and were used to identify those with a higher probability of a positive molecular diagnosis. CONCLUSIONS: We developed an easy and fast screening method that takes into account only clinical data that can help to select the patients with a high probability of positive genetic results from molecular sequencing of Brazilian HCM patients.

Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HC) is the most prevalent genetic cardiac disease caused by a mutation in sarcomeres, Z-disks, or calcium-handling genes and is characterized by unexplained left ventricular hypertrophy. The aim of this study was to determine the genetic profile of Brazilian patients with HC and correlate the genotype with the phenotype. METHODS: We included 268 index patients from São Paulo city and 3 other cities in Brazil and extracted their DNA from whole blood. We amplified the coding sequencing of MYH7, MYBPC3, and TNNT2 genes and sequenced them with an automatic sequencer. RESULTS: We identified causal mutations in 131 patients (48.8%). Seventy-eight (59.5%) were in the MYH7 gene, 50 (38.2%) in the MYBPC3 gene, and 3 (2.3%) in the TNNT2 gene. We identified 69 mutations, 24 not previously described. Patients with an identified mutation were younger at diagnosis and at current age, had a higher mean heart rate and higher nonsustained ventricular tachycardia frequency compared with those without a mutation. Patients with MYH7 gene mutations had a larger left atrium and higher frequency of atrial fibrillation than did patients with MYBPC3 gene mutations. CONCLUSION: The presence of a mutation in one of the genes suggests a worse prognosis. Mutations in the MYH7 gene, rather than in the MYBPC3 gene, were also related to a worse prognosis. This is the first work characterizing HC molecular epidemiology in the Brazilian population for the 3 most important genes.

Type 1 cardiorenal syndrome in a patient with an acute infection caused by Trypanosoma cruzi in the Brazilian Amazon region - a case report.

Cardiorenal syndrome type 1 (CRS 1) occurs when acute heart failure leads to acute kidney injury. There are several etiologies of CRS 1, including Chagas disease. Here, we present the first case report of CRS 1 in a patient with acute Chagas disease. Electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging showed signs of acute myocarditis. Laboratory examination revealed severe loss of kidney function, with a creatinine clearance of 30 mL/min, which fully normalized after treatment. Due to emergence of Chagas disease in the Brazilian Amazon, it is important to report unique clinical features in order to improve patients' outcomes.

Dysregulation of Autonomic Nervous System in Chagas' Heart Disease Is Associated with Altered Adipocytokines Levels.

BACKGROUND: Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. METHODS AND RESULTS: Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. CONCLUSIONS: We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease.

Trypanosoma cruzi strain TcI is associated with chronic Chagas disease in the Brazilian Amazon.

BACKGROUND: Chagas disease in the Amazon region is considered an emerging anthropozoonosis with a predominance of the discrete typing units (DTUs) TcI and TcIV. These DTUs are responsible for cases of acute disease associated with oral transmission. Chronic disease cases have been detected through serological surveys. However, the mode of transmission could not be determined, or any association of chronic disease with a specific T. cruzi DTU's. The aim of this study was to characterize Trypanosoma cruzi in patients with chronic Chagas disease in the State of Amazonas, Brazil. METHODS: Blood culture and xenodiagnosis were performed in 36 patients with positive serology for Chagas disease who participated in a serological survey performed in urban and rural areas of Manaus, Amazonas. DNA samples were extracted from the feces of triatomines used for xenodiagnosis, and the nontranscribed spacer of the mini-exon gene and the mitochondrial gene cytochrome oxidase subunit II (COII) were amplified by PCR and sequenced. RESULTS: Blood culture and xenodiagnosis were negative in 100% of samples; however, molecular techniques revealed that in 13 out of 36 (36%) fecal samples from xenodiagnosis, T. cruzi was characterized as the DTU TcI, and different haplotypes were identified within the same DTU. CONCLUSION: The DTU TcI, which is mainly associated with acute cases of Chagas disease in the Amazon region, is also responsible for chronic infection in patients from a region in the State of Amazonas.

Leptin in heart failure.

INTRODUCTION: In the study of heart failure (HF), biomarkers have served as an important tool for diagnostic, therapeutic and prognostic assessment. Their main categories in the area of HF are markers of ventricular dysfunction, inflammation, metabolism, neurohormones, oxidative stress, myocardial injury and extracellular matrix remodeling. AREAS COVERED: Leptin contributes to the modulation of metabolism, respiratory control and inflammation, which are factors associated with cardiovascular disease. Serum levels of leptin in patients with HF have shown conflicting results in previous studies. Most studies have suggested that serum leptin levels may be increased in patients without cachexia. On the other hand, leptin levels are decreased in patients with advanced HF and cardiac cachexia or specific HF etiologies such as Chagas' disease. Other studies have showed that leptin levels were related to exercise intolerance. The only exception of the direct correlation of serum leptin levels with severity of CHF is present in CHF with cardiac cachexia, because patients with cardiac cachexia have plasma leptin concentrations lower than those without cardiac cachexia. EXPERT OPINION: These findings can make leptin an important diagnostic and prognostic marker for HF and be included in routine investigation of patients with HF.

Type 1 cardiorenal syndrome in a patient with an acute infection caused by Trypanosoma cruzi in the Brazilian Amazon region - a case report

Abstract Cardiorenal syndrome type 1 (CRS 1) occurs when acute heart failure leads to acute kidney injury. There are several etiologies of CRS 1, including Chagas disease. Here, we present the first case report of CRS 1 in a patient with acute Chagas disease. Electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging showed signs of acute myocarditis. Laboratory examination revealed severe loss of kidney function, with a creatinine clearance of 30 mL/min, which fully normalized after treatment. Due to emergence of Chagas disease in the Brazilian Amazon, it is important to report unique clinical features in order to improve patients' outcomes.

New diagnostic serum biomarkers for Chagas disease.

INTRODUCTION: Chagas disease (CD) is the major cause of morbidity and mortality in many regions of Latin America, and its importance has increased in other regions of the world owing to the global migration phenomenon. AREAS COVERED: This article evaluates the application of heart failure, inflammatory and metabolic biomarkers in the clinical management of CD through a detailed review of the medical literature. Through this, the reader is shown that the identification of biomarkers is necessary not only to improve understanding of the pathophysiology of the disease, but also for prognostic stratification and therapeutic monitoring. EXPERT OPINION: The poor prognosis of CD cardiomyopathy when compared with non-inflammatory cardiomyopathies as well as the lack of effective drugs for its treatment elucidates the need for new diagnostic and therapeutic strategies. The use of biomarkers in CD may allow us to improve the prognosis and target individuals at higher risk who need more intensive and earlier treatment.

Alterações ao Doppler tecidual em pacientes com a forma aguda da doença de chagas / Alterations to tissue Doppler in patients with acute form of chagas disease

Fundamento: Recentemente tem ocorrido aumento do número de casos agudos de doença de Chagas, principalmente causados por transmissão oral. A maioria dos pacientes mostra boa evolução, apresentando sintomatologia compatívelcom processo infeccioso sistêmico, porém sem alterações cardíacas significativas ao exame físico, eletrocardiograma eecocardiograma transtorácico.Objetivo: Avaliar alterações ecocardiográficas com análise do Doppler tecidual em pacientes com doença de Chagas aguda. Métodos: Foram avaliados pacientes com diagnóstico de doença de Chagas aguda confirmada por exame parasitológico direto. Esses pacientes foram submetidos a exame físico, eletrocardiograma e ecocardiograma transtorácico, sendocomparados com um grupo controle.Resultados: Foram avaliados 12 casos com doença de Chagas aguda e 15 indivíduos no grupo controle. As variáveis que apresentaram diferenças significativas foram: ondas S’ lateral de VE (DCA = 0,09 ± 0,02 m/seg; GC = 0,11 ± 0,02 m/seg; p = 0,024); E’ lateral (DCA = 0,13 ± 0,03 m/seg; GC = 0,18 ± 0,03 m/seg; p = 0,001); E’ septal do VE (DCA = 0,10± 0,03 m/seg; GC = 0,14 ± 0,03 m/seg; p = 0,008), A’ lateral do VE (DCA = 0,08 ± 0,03 m/seg; GC = 0,12 ± 0,01 m/seg;p = 0,003), onda S’ do VD (DCA = 0,12 ± 0,02 m/seg; GC = 0,17 ± 0,02 m/seg; p < 0,001) e TAPSE (DCA = 1,95 ±0,41 cm; GC = 2,37 ± 0,25 cm; p = 0,006). Conclusões: Em pacientes com doença de Chagas aguda, mesmo quando apresentam evolução benigna, podem ocorrer alterações subclínicas detectadas principalmente ao Doppler tecidual. Essas alterações podem ser importantes na avaliação do tratamento da fase aguda e na sua evolução a longo prazo.

Background: Recently there has been an increased number of cases of acute Chagas disease primarily caused by oral transmission. Most patients have a good outcome, presenting symptoms consistent with systemic infectious process, but no significant cardiac abnormalities on physical examination, electrocardiogram and echocardiogram.Objective: To evaluate echocardiographic changes with tissue Doppler analysis in patients with acute Chagas disease.Methods: We evaluated patients with acute Chagas disease confirmed by cytological examination. These patients underwent a physical examination, eletrocardiogram and transthoracic echocardiography, and compared with a control group. Results: We evaluated 12 patients with acute Chagas disease and 15 subjects in the control group. Variables that showed significant diferences were waves S ‘side of LV (DCA = 0.09 ± 0.02m/sec; CG = 0.11 ± 0.02 m/sec; p = 0.024); and ‘side (DCA = 0.13 ± 0.03 m/sec; CG = 0.18 ±0.03 m/sec; p = 0.001); Septal E ‘LV (DCA = 0.10 ± 0.03 m/sec; CG = 0.14 ± 0.03 m/sec; p = 0.008), A’ lateral LV (DCA = 0.08 ± 0.03 m/sec;CG = 0 12 ± 0.01 m/sec; p = 0,003), S wave ‘RV (DCA = 0.12 ± 0.02 m/sec; CG = 0.17 ± 0.02 m/sec; p < 0.001) and TAPSE (DCA = 1,95cm ± 0.41; CG = 2.37 ± 0.25 cm; p = 0.006). Conclusions: In patients with acute Chagas disease, even when present benign, there may be subclinical alterations detected primarilyby tissue Doppler. These changes may be important in the treatment of acute and its long-term evolution.

[Stroke in a chronic autochthonous chagasic patient from the Brazilian Amazon]. / Acidente vascular encefálico isquêmico em paciente chagásico crônico autóctone da Amazônia Brasileira.

An episode of stroke in a chronic autochthonous chagasic patient from the Brazilian Amazon is reported. This is the first documented case of a predominantly thromboembolic form of chronic Chagasic cardiopathy in the region.

[Cardiac involvement in Acute Chagas' Disease cases in the Amazon region].

The cardiac involvement of five patients from the Amazon region with Acute Chagas' Disease (ACD) is described. Four of these patients presented probable oral transmission. All of them presented some degree of cardiac involvement, but there were no deaths.