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1.
Parasit Vectors ; 12(1): 260, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126327

RESUMO

BACKGROUND: Chagas disease is a protozoan infection caused by Trypanosoma cruzi. The disease has a chronic course in which 20-30% of the patients would develop progressive damage to the cardiovascular system and the gastrointestinal tube. We are still unable to predict who will develop end-organ damage but there are some acquired and genetic risk factors already known. RESULTS: We reviewed data from 833 patients with serologically confirmed Chagas disease in this retrospective study. Patients were classified as siblings or non-siblings (controls) and the results of pre-treatment blood PCR assay, end-organ damage (cardiac and/or gastrointestinal), and the presence of delayed type hypersensitivity (DTH) skin involvement in patients treated with benznidazole were analyzed. Siblings were grouped by family and we randomly generated groups of 2 or 3 persons with the remaining controls. We classified the results of each variable as concordant or discordant and compared the concordance in these results among the sibling groups with that among control groups. We identified 71 groups of siblings and randomly generated 299 groups of non-related patients. Pre-treatment blood PCR concordance was significantly higher (19%) among siblings compared to controls (P = 0.02), probably due to a higher frequency in pre-treatment positive results. No other statistically significant differences were found. CONCLUSIONS: A significant difference was found in the concordance of pre-treatment blood PCR for T. cruzi among siblings compared to non-related controls.


Assuntos
Doença de Chagas/etnologia , Doença de Chagas/genética , Irmãos , Adulto , Bolívia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/etiologia , Doença de Chagas/complicações , Doença Crônica , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/parasitologia , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi
2.
Am J Trop Med Hyg ; 100(1): 93-96, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30526728

RESUMO

Chagas disease (CD), caused by infection with the parasite Trypanosoma cruzi, leads to severe cardiomyopathy in 20-30% of patients, whereas the remainder may stay asymptomatic and never develop cardiomyopathy or other clinical manifestations. The underlying cause for this variable outcome is not fully characterized, although previous studies have found high levels of circulating mannose-binding lectin (MBL) to be associated with cardiac failure echocardiographic changes. We report three indeterminate (asymptomatic) chronic Chagas patients who were followed up for 10 years. Two of these patients developed chronic chagasic cardiomyopathy (CCC) during this follow-up period and, when genotyped, were found to be carriers of the high MBL producer HYPA/HYPA genotype, suggesting that genetically determined high MBL serum might be associated with the risk of CCC development. These results suggest the use of MBL quantification and MBL2 genotyping as tools for clinical assessment in patients with chronic CD.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Progressão da Doença , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/genética , Idoso , Infecções Assintomáticas , Brasil , Cardiomiopatia Chagásica/etiologia , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Trypanosoma cruzi
3.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

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.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
4.
Rev Inst Med Trop Sao Paulo ; 60: e73, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30462796

RESUMO

Visceral leishmaniasis (VL) is an endemic parasitic disease frequently found in Northeast Brazil and may cause acute kidney injury (AKI) and glomerulonephritis. After appropriate treatment, renal function recovery may occur. We describe the rare case of a patient with VL, who developed severe AKI requiring dialysis and was subsequently diagnosed with Chagas disease coinfection. After specific treatment for VL, there was partial recovery of the renal function, followed by the onset of Chagas disease cardiomyopathy.


Assuntos
Lesão Renal Aguda/parasitologia , Cardiomiopatia Chagásica/complicações , Glomerulonefrite/parasitologia , Leishmaniose Visceral/complicações , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/patologia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/patologia , Coinfecção , Glomerulonefrite/diagnóstico , Glomerulonefrite/patologia , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade
6.
Circulation ; 138(12): e169-e209, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30354432

RESUMO

BACKGROUND: Chagas disease, resulting from the protozoan Trypanosoma cruzi, is an important cause of heart failure, stroke, arrhythmia, and sudden death. Traditionally regarded as a tropical disease found only in Central America and South America, Chagas disease now affects at least 300 000 residents of the United States and is growing in prevalence in other traditionally nonendemic areas. Healthcare providers and health systems outside of Latin America need to be equipped to recognize, diagnose, and treat Chagas disease and to prevent further disease transmission. METHODS AND RESULTS: The American Heart Association and the Inter-American Society of Cardiology commissioned this statement to increase global awareness among providers who may encounter patients with Chagas disease outside of traditionally endemic environments. In this document, we summarize the most updated information on diagnosis, screening, and treatment of T cruzi infection, focusing primarily on its cardiovascular aspects. This document also provides quick reference tables, highlighting salient considerations for a patient with suspected or confirmed Chagas disease. CONCLUSIONS: This statement provides a broad summary of current knowledge and practice in the diagnosis and management of Chagas cardiomyopathy. It is our intent that this document will serve to increase the recognition of Chagas cardiomyopathy in low-prevalence areas and to improve care for patients with Chagas heart disease around the world.


Assuntos
Cardiomiopatia Chagásica/terapia , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , American Heart Association , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/epidemiologia , Cardiomiopatia Chagásica/parasitologia , Humanos , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Resultado do Tratamento , Tripanossomicidas/efeitos adversos , Trypanosoma cruzi/isolamento & purificação , Estados Unidos
7.
Curr Cardiol Rep ; 20(12): 131, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30311008

RESUMO

PURPOSE OF REVIEW: Chagas cardiomyopathy is an emerging form of non-ischemic cardiomyopathy in the USA. This review aims to summarize current concepts in pathophysiology, disease transmission, medical therapy, and heart transplantation for patients with chronic Chagas cardiomyopathy. RECENT FINDINGS: The incidence of Chagas cardiomyopathy is increasing in the USA, driven mainly by immigration from countries where Chagas disease is endemic. Chagas cardiomyopathy is a chronic, progressive myocarditis, with hallmark features of biventricular dysfunction, ventricular arrhythmias, thromboembolic complications, and a high risk of mortality. Currently, there is no effective treatment for chronic Chagas cardiomyopathy. Heart transplantation is the only treatment for patients with end-stage Chagas cardiomyopathy, but is associated with unique challenges including risk of reactivation. As the prevalence of Chagas cardiomyopathy increases in the USA, practitioners must be aware of the unique challenges in diagnosis and management that Chagas cardiomyopathy presents.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/epidemiologia , Cardiomiopatia Chagásica/terapia , Trypanosoma cruzi/isolamento & purificação , Fármacos Cardiovasculares/uso terapêutico , Doença de Chagas/epidemiologia , Transplante de Coração/efeitos adversos , Humanos , Miocardite/etiologia , Fatores de Risco , Resultado do Tratamento , Tripanossomicidas/uso terapêutico , Estados Unidos/epidemiologia
8.
J Card Surg ; 33(10): 597-602, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30215853

RESUMO

Although Chagas disease is a rare entity in North America, it is associated with significant cardiac morbidity. It is estimated that 20-30% of those who are infected will eventually develop cardiovascular disease secondary to Chagas disease. We review the literature and share our experience on the surgical management of this challenging patient population.


Assuntos
Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/cirurgia , Aneurisma Cardíaco/etiologia , Aneurisma Cardíaco/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiomiopatia Chagásica/diagnóstico , Ecocardiografia , Feminino , Aneurisma Cardíaco/diagnóstico por imagem , Ventrículos do Coração , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Nifurtimox , Nitroimidazóis , Testes Sorológicos , Volume Sistólico , Resultado do Tratamento , Tripanossomicidas
10.
Trials ; 19(1): 507, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30231899

RESUMO

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.


Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Suplementos Nutricionais , Selenito de Sódio/uso terapêutico , Adolescente , Adulto , Idoso , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Suplementos Nutricionais/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Selenito de Sódio/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
11.
Rev Soc Bras Med Trop ; 51(4): 557-559, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30133646

RESUMO

Chagas disease is a chronic parasitological disease, which could cause cardiac manifestations in approximately one-third of affected individuals. Benznidazole and nifurtimox are used to treat this parasitological infection caused by Trypanosoma cruzi. Conventionally, the criterion for cure is consistently negative serological tests after treatment. We report a case of a patient who was treated when she was 13 years old and achieved T. cruzi negative seroconversion but developed Chagas disease cardiomyopathy as an adult.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Doença de Chagas/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Nitroimidazóis/uso terapêutico , Recidiva , Tripanossomicidas/uso terapêutico
12.
Europace ; 20(11): 1813-1818, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29509903

RESUMO

Aims: Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. Methods and results: This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. Conclusion: This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.


Assuntos
Terapia de Ressincronização Cardíaca , Cardiomiopatia Chagásica , Brasil/epidemiologia , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Desfibriladores Implantáveis , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico
13.
Clin Infect Dis ; 67(4): 519-524, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29438471

RESUMO

Background: Trypanosoma cruzi causes Chagas disease in the Americas. The outcome of infection ranges from lifelong asymptomatic status to severe disease. Relationship between T. cruzi lineage (TcI-TcVI) infection history and prognosis is not understood. We previously described peptide-based lineage-specific enzyme-linked immunosorbent assay (ELISA) with trypomastigote small surface antigen (TSSA). Methods: A novel rapid diagnostic test (RDT; Chagas Sero K-SeT) that incorporates a peptide that corresponds to the TSSA II/V/VI common epitope was developed and validated by comparison with ELISA. Patients from Bolivia and Peru, including individuals with varying cardiac pathology, and matched mothers and neonates, were then tested using Chagas Sero K-SeT. Results: Chagas Sero K-SeT and ELISA results, with a Bolivian subset of cardiac patients, mothers, and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) with class B (electrocardiogram suggestive of Chagas cardiomyopathy) and class C/D (decreased left ventricular ejection fraction; moderate/severe Chagas cardiomyopathy) revealed a statistically significant increase in Chagas Sero K-SeT reactivity with increasing severity (χ2 for trend, 7.39; P = .007). In Peru, Chagas Sero K-SeT detected the sporadic TcII/V/VI infections. Conclusions: We developed a low cost RDT that can replace ELISA for identification of TSSA II/V/VI immunoglobulin G. Most importantly, we show that response to this RDT is associated with severity of Chagas cardiomyopathy and thus may have prognostic value. Repeated challenge with T. cruzi infection may both exacerbate disease progression and boost the immune response to the TSSApep-II/V/VI epitope.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Testes Sorológicos/métodos , Índice de Gravidade de Doença , Trypanosoma cruzi/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Protozoários/imunologia , Bolívia , Ensaio de Imunoadsorção Enzimática , Feminino , Sangue Fetal/parasitologia , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Peru , Testes Sorológicos/economia , Adulto Jovem
14.
Int J Cardiol ; 250: 260-265, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29079412

RESUMO

BACKGROUND: Chronic Chagas cardiomyopathy (CCC) is the most serious and frequent manifestation of Chagas disease. Conduction abnormalities and bradycardia requiring pacemaker are common. The aim of this study was to determine the rate and predictors of death in CCC patients with pacemaker. METHODS: In this single-center prospective cohort study we assessed the outcome of 396 CCC patients with pacemaker, followed-up for at least 24months. All patients underwent a clinical and device assessment, 12-lead electrocardiography and echocardiography. RESULTS: During the median follow-up of 1.9years (Interquartile range 1.6-2.4), there were 65 (16.4%) deaths, yielding an annual mortality rate of 8.6%. The major cause was sudden death (33.8%), followed by heart failure (HF), 32.3%. All the investigated variables were examined as potential predictors of death. The final multivariate logistic regression model included five independent variables: advanced HF functional class (OR [odds ratio] 6.71; 95% confidence interval [95% CI] 1.95-23.2; P=0.003), renal disease (OR 5.71; 95% CI 1.80-18.0; P=0.003), QRS ≥150ms (OR 2.80; 95% CI 1.08-7.27; P=0.034), left atrial enlargement (OR 2.75; 95% CI 1.09-6.95; P=0.032) and left ventricular ejection fraction ≤43% (OR 2.31; 95% CI 1.07-4.97; P=0.032). The model had good discrimination, confirmed by bootstrap validation (optimism-adjusted c-statistic of 0.78) and the calibration curve showed a proper calibration (slope=0.972). CONCLUSIONS: CCC patients with pacemaker have a high annual mortality rate despite that the pacemaker related variables were not predictors of death. The independent predictors of death can help us to identify the poor prognosis patients.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/mortalidade , Marca-Passo Artificial/tendências , Idoso , Doença Crônica , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Valor Preditivo dos Testes , Estudos Prospectivos
15.
Salvador; s.n; 2018. 85 p. ilus, tab.
Tese em Português | LILACS | ID: biblio-1005571

RESUMO

INTRODUÇÃO: A doença de Chagas é uma doença parasitária causada pelo Trypanosoma cruzi, a qual representa uma das principais causas de morbimortalidade na América Latina. As intervenções terapêuticas existentes não são totalmente eficazes, sendo o transplante cardíaco a única alternativa para os pacientes com cardiopatia chagásica crônica (CCC) grave. Neste sentido, a ausência de terapias capazes de atuar diretamente sobre os determinantes fisiopatológicos da doença torna necessária a identificação de novas abordagens terapêuticas. Estudos previamente realizados pelo nosso grupo mostraram que a utilização de célulastronco obtidas da medula óssea e de outras fontes teve efeitos benéficos no tratamento da CCC experimental. A possibilidade de potencializar os efeitos parácrinos das células-tronco através de modificação genética tem sido alvo de investigações científicas. OBJETIVO: Avaliar os efeitos da terapia com células-tronco mesenquimais (CTMs) da medula óssea, modificadas geneticamente para superexpressar o fator estimulador de colônias de granulócitos (hG-CSF) ou o fator de crescimento semelhante à insulina 1 (hIGF-1) em um modelo experimental de CCC. MATERIAL E MÉTODOS: Camundongos C57BL/6 foram infectados com 1000 tripomastigotas da cepa Colombiana de T. cruzi e, após seis meses de infecção, foram tratados com CTM, CTM-G-CSF, ou CTM-IGF-1. Grupos de animais não infectados ou infectados tratados com salina (veículo) foram utilizados como controles. Todos os animais foram eutanasiados sob anestesia após dois meses de tratamento para análises histopatológicas e morfométricas do coração ou músculo esquelético, bem como para avaliação da expressão de citocinas inflamatórias. RESULTADOS: As secções de corações de camundongos dos grupos tratados com CTM, CTM-GCSF ou CTM-IGF-1 apresentaram redução significativa do número de células inflamatórias e do percentual de fibrose em comparação aos animais chagásicos tratados com salina, sendo esta diferença mais evidente no grupo que foi tratado com células-tronco que superexpressam o G-CSF. Além disto, a terapia com CTM-G-CSF induziu a mobilização de células imunomoduladoras para o coração, tais como células supressoras de origem mielóide (MDSC) e células T regulatórias Foxp3+ que expressam IL-10. A avaliação da expressão gênica das citocinas inflamatórias no tecido cardíaco mostrou um aumento das citocinas inflamatórias em animais chagásicos crônicos quando comparados aos controles não infectados, sendo a maioria delas moduladas de forma significativa nos grupos que foram tratados com CTM ou CTM-G-CSF. Apesar da terapia utilizando CTM-IGF-1 não ter apresentado benefício adicional ao tecido cardíaco comparado ao grupo que foi tratado com CTM não modificadas, foi observado um efeito regenerativo desta terapia no músculo esquelético dos animais, resultando em um aumento de fibras musculares esqueléticas 60 dias após o tratamento. CONCLUSÃO: Nossos resultados demonstram que o tratamento com CTM da medula óssea que superexpressam hG-CSF ou hIGF-1 potencializou o efeito terapêutico das CTMs através de ações imunomoduladoras e pró-regenerativas no coração e músculo esquelético de camundongos cronicamente infectados por T. cruzi. Desse modo, a modificação genética de CTMs para superexpressão de fatores com potencial terapêutico representa uma estratégia promissora para o desenvolvimento de novas terapias para a cardiomiopatia chagásica crônica


INTRODUCTION: Chagas' disease is a parasitic disease caused by Trypanosoma cruzi, which is one of the main causes of cardiovascular morbidity and mortality in Latin America. Existing therapeutic interventions are not fully effective, and heart transplantation is the only alternative for patients with severe chronic Chagas' heart disease. In this sense, the absence of therapies capable of acting directly on the pathophysiological determinants of the disease demonstrates the necessity of identifying new therapeutic approaches. Studies previously conducted by our group demonstrated that the use of stem cells obtained from bone marrow and other sources had beneficial effects in the treatment of experimental chagas disease. Additionally, the possibility of enhancing stem cell paracrine effects through genetic modification has been the subject of scientific investigations. OBJECTIVE: To evaluate the effects of genetically modified mesenchymal stem cell therapy to overexpress granulocyte colony stimulating factor (hG-CSF) or insulin-like growth factor 1 (hIGF-1) in an experimental model of Chagas disease. MATERIAL AND METHODS: C57BL/6 mice were infected with 1000 trypomastigotes from the Colombian strain of T. cruzi and, after six months of infection, were treated with CTM, CTM-G-CSF, or CTM-IGF-1. Groups of uninfected or infected animals treated with saline (vehicle) were used as controls. All animals were euthanized under anesthesia after two months of treatment for histopathological and morphometric analysis of the heart or skeletal muscle, as well as for evaluation of inflammatory cytokine expression. RESULTS: Mouse heart sections from groups treated with CTM, CTM-GCSF or CTM-IGF-1 showed a significant reduction in the number of inflammatory cells and the percentage of fibrosis when compared to chagasic animals treated with saline.This difference was more evident in the group that was treated with stem cells overexpressing G-CSF. In addition, CTM-G-CSF therapy induced mobilization of immunomodulatory cells to the heart, including myeloid suppressor cells (MDSC) and Foxp3 + regulatory T cells expressing IL-10. Expression of inflammatory cytokine genes in cardiac tissue revealed an increase in inflammatory cytokines in chronic chagasic animals when compared to uninfected controls, where most cytokines were significantly modulated in groups treated with CTM or CTM-G-CSF. Although CTM-IGF-1 therapy demonstrated no additional benefit to cardiac tissue when compared to the group treated with unmodified CTM, a regenerative effect of this therapy was observed in chagasic mice skeletal muscle, resulting in an increase in skeletal muscle fibers 60 days after treatment. CONCLUSION: Our results demonstrate that bone marrow derived CTM treatment overexpressing hG-CSF or hIGF-1 enhanced the therapeutic effects of MSCs through immunomodulation and proregenerative actions in the heart and skeletal muscle of mice chronically infected wthT. cruzi. Thus, the genetic modification of CTMs for overexpression of factors with therapeutic potential represents a promising strategy for the development of new therapies for chronic chagasic cardiomyopathy


Assuntos
Humanos , Células-Tronco/imunologia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/terapia
16.
Artigo em Inglês | MEDLINE | ID: mdl-29133379

RESUMO

BACKGROUND: Chagasic cardiomyopathy (CC) is the most frequent nonischemic substrate causing left ventricular (LV) tachycardia in Latin America. Systematic characterization of the LV epicardial/endocardial scar distribution and density in CC has not been performed. Additionally, the usefulness of unipolar endocardial electroanatomic mapping to identify epicardial scar has not been assessed in this setting. METHODS AND RESULTS: Nineteen patients with CC undergoing detailed epicardial and endocardial LV tachycardia mapping and ablation were included. A total of 8494 epicardial and 6331 endocardial voltage signals and 314 epicardial/endocardial matched pairs of points were analyzed. Basal lateral LV scar involvement was observed in 18 of 19 patients. Bipolar voltage mapping demonstrated larger epicardial than endocardial scar and core-dense (≤0.5 mV) scar areas (28 [20-36] versus 19 [15-26] and 21 [2-49] versus 4 [0-7] cm2; P=0.049 and P=0.004, respectively). Bipolar epicardial and endocardial voltages within scar were low (0.4 [0.2-0.55] and 0.54 [0.33-0.87] mV, respectively) and confluent, indicating a dense/transmural scarring process in CC. The endocardial unipolar voltage value (with a newly proposed ≤4-mV cutoff) predicted the presence and extent of epicardial bipolar scar (P<0.001). CONCLUSIONS: CC causes a unique ventricular tachycardia substrate concentrated to the basal lateral LV, with marked epicardial predominance. The scar pattern is particularly dense and transmural as compared with the more erratic/patchy scar patterns seen in other nonischemic cardiomyopathies. Endocardial unipolar voltage mapping serves to characterize epicardial scar in this setting.


Assuntos
Potenciais de Ação , Cardiomiopatia Chagásica/complicações , Cicatriz/etiologia , Endocárdio/fisiopatologia , Mapeamento Epicárdico , Miocárdio/patologia , Pericárdio/fisiopatologia , Taquicardia Ventricular/diagnóstico , Idoso , Ablação por Cateter , Cardiomiopatia Chagásica/diagnóstico , Cicatriz/diagnóstico , Endocárdio/patologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/cirurgia
17.
J Am Coll Cardiol ; 70(12): 1510-1524, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28911515

RESUMO

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.


Assuntos
Cardiomiopatia Chagásica/etiologia , Cardiomiopatia Chagásica/terapia , Arritmias Cardíacas/etiologia , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/diagnóstico , Doença Crônica , Insuficiência Cardíaca/etiologia , Humanos , Prognóstico
19.
J Stroke Cerebrovasc Dis ; 26(12): 2864-2869, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28844546

RESUMO

BACKGROUND: Cardioembolism is considered a major pathophysiological mechanism in patients with ischemic stroke (IS) and Chagas disease (CD). However, a previous study reported that other stroke subtypes are present in more than 40% of CD patients according to the TOAST classification. Therefore, the aim of our study was to evaluate the etiologic classification of stroke in patients with CD using the Causative Classification System (CCS), the ASCOD, and the TOAST classifications in a prospective cohort of patients. METHODS: Patients evaluated in our outpatient clinic from 2012 to 2015 with IS and CD were included and underwent full investigation for stroke etiology. TOAST, CCS TOAST, and the ASCOD classifications were compared. FINDINGS: We Included 32 patients (18 men; mean age 62.7 +/-10.1 years). A total of 93.8% had at least 1 vascular risk factor; the most frequent was hypertension (87.5%). According to TOAST, we defined 87.5% as having cardioembolic stroke, being 9.4% as large-artery atherosclerotic (LAA) and 3.1% as undetermined cause. Using the CCS TOAST, 62.5% were classified as cardioaortic embolism evident and 15.6% as possible, 6.3% as small artery occlusion evident and 3.1% as probable, and 12.5% as LAA evident. When ASCOD phenotyping was applied, atherosclerosis was present in 50.1% of patients (A1 = 6.3%, A3 = 43.8%), cardiac pathology in 84.4% (C1 = 62.5%, C2 = 15.6%, C3 = 6.3%), and small-vessel disease in 66% (S1 = 9.4%, S2 = 3.1%, S3 = 3.1%). FINDINGS: In conclusion, the use of the CCS and the ASCOD phenotyping in patients with CD confirmed a high frequency of cardioembolic IS but also showed that other etiologies are prevalent, such as large-artery atherosclerosis and small-vessel occlusion.


Assuntos
Cardiomiopatia Chagásica/epidemiologia , Técnicas de Apoio para a Decisão , Embolia Intracraniana/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Brasil/epidemiologia , Cardiomiopatia Chagásica/diagnóstico , Feminino , Humanos , Embolia Intracraniana/classificação , Embolia Intracraniana/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Fenótipo , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo
20.
Int J Cardiol ; 244: 206-212, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28676242

RESUMO

We have uncovered 80 medical files corresponding to original cases of Chagas' disease used for the classical description of the acute and cardiac forms of the disease. Sixty of them were diagnosed cardiac forms of the disease. The detailed clinical description of these 60 files is in excellent agreement with the nosography of progressive heart disease given by Chagas in his original 1922 paper. The reports we had access to, characterize a novel form of cardiac disease, dominated by progressive AV block, enlargement and displacement of the heart and sudden death, in relatively young adults including juveniles. In contrast to that remarkable clinical description, the assertion made by Chagas that this set of clinical signs was the consequence of an earlier infection by Trypanosoma cruzi rests on weak evidence, due to the difficulty to identify the parasite in most patients. Moreover, the association of thyroid dysfunction with cardiac disease emphasized by Chagas cannot be deduced from the files we have examined. Finally, the main reason why the disease had not been recognized for long as a defined clinical entity, is likely the absence of markedly distinctive clinical signs compared to most other parasitic diseases, poor sanitary conditions and the probable lack of clinical skills of the rare doctors working in the area where the disease was described.


Assuntos
Arquivos , Cardiomiopatia Chagásica/história , Registros Médicos , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , História do Século XX , Humanos , Trypanosoma cruzi
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