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1.
Life Sci ; 230: 141-149, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129142

RESUMO

When administered alone, preinfection exercise training and benznidazole-based chemotherapy induce cardioprotection in Chagas disease. However, the effect of concomitant exercise and benznidazole treatment is unknown. We investigated whether exercise and specific chemotherapy could interact to modulate parasitemia, inflammation, redox status and heart damage in a murine model of T. cruzi infection. Wistar rats were randomized into an uninfected control group (CNT) and four groups infected with T. cruzi: sedentary untreated (SUN) and treated (STR), and trained untreated (TUN) and treated (TTR). Running training was administered 5 days/week for 4 weeks. Treated animals concomitantly received 100 mg/kg/day benznidazole. Heart inflammation and reactive damage were not detected in CNT animals. Compared to SUN, TUN animals presented increased levels of parasitemia, myocarditis, nitric oxide, hydrogen peroxide, protein carbonyl, malondialdehyde, cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10 and IL-17), catalase, superoxide dismutase and glutathione reductase activity, as well as reduced heart non-protein antioxidant levels (P < 0.05). TTR animals exhibited higher levels of parasitemia, myocarditis, hydrogen peroxide, malondialdehyde, IFN-γ, TNF-α and IL-6 than STR animals (P < 0.05), which showed the lowest levels of all analyzed parameters compared to the other groups (P < 0.05). Our findings indicate that exercise aggravates acute infection. When concomitantly administered with benznidazole, exercise training impaired parasitic control and chemotherapy-induced cardioprotection in T. cruzi-infected rats. Considering that exercise training and T. cruzi infection constitute independent metabolic challenges, the negative effects of concomitant treatment are potentially related to the overlapping oxidative and immunoinflammatory demands of exercise and the infection itself.


Assuntos
Doença de Chagas/tratamento farmacológico , Doença de Chagas/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Antioxidantes/farmacologia , Cardiotônicos/metabolismo , Catalase/metabolismo , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Citocinas/metabolismo , Modelos Animais de Doenças , Coração/fisiologia , Inflamação/metabolismo , Interleucina-10/metabolismo , Masculino , Miocardite/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Nitroimidazóis/farmacologia , Parasitemia/parasitologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/metabolismo
2.
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
3.
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
4.
RELAMPA, Rev. Lat.-Am. Marcapasso Arritm ; 31(4): 133-137, out.-dez. 2018.
Artigo em Espanhol | LILACS | ID: biblio-999084

RESUMO

A Doença de Chagas atinge milhões de pessoas na América Latina e a evolução para cardiopatia crônica tem como seu principal desfecho a morte súbita cardíaca (MSC). Neste artigo, revisamos, sob a luz da medicina baseada em evidências, os principais aspectos sobre marcadores prognósticos clínicos e de imagem (especificamente a análise da fibrose em ressonância magnética) e terapêutica existente no tratamento e prevenção da MSC, como terapia farmacológica, evidências sobre dispositivos implantáveis e tratamento invasivo de arritmias ventriculares


Chagas disease affects millions of people in Latin America and its evolution to heart disease has the sudden cardiac death (SCD) as one main outcome. In this article, we sought to review the essential evidence-based aspects about prognostic markers and treatments for SCD, including farmacological treatment, use of implantable devices and invasive treatment of ventricular arrhthymias


Assuntos
Humanos , Masculino , Feminino , Cardiomiopatia Chagásica/terapia , Morte Súbita Cardíaca/prevenção & controle , Doença de Chagas , Prognóstico , Volume Sistólico , Trypanosoma cruzi/imunologia , Espectroscopia de Ressonância Magnética/métodos , Doença Crônica , Taquicardia Ventricular , Desfibriladores Implantáveis , Tratamento Farmacológico/métodos
5.
RELAMPA, Rev. Lat.-Am. Marcapasso Arritm ; 31(4): 167-172, out.-dez. 2018. tab, ilus
Artigo em Português | LILACS | ID: biblio-999253

RESUMO

Introdução: A cardiopatia chagásica crônica (CCC) engloba complexo espectro de apresentações, não sendo incomuns episódios de morte arrítmica em portadores de função ventricular esquerda preservada (FVEP) ou quase normal (FVEQN). Métodos: Avaliação retrospectiva de 7 portadores de CCC por 4 anos, com FVEP, submetidos a implante de cardiodesfibrilador implantável (CDI) devido taquicardia ou fibrilação ventricular (TV/FV). Foram realizadas avaliações clínica, estrutural e eletrocardiográfica. Resultados: Idade média: 57,5±4,45 anos e 71,4% do sexo masculino. Função ventricular esquerda (FVE) inicial foi de 56,14%±4,45, com alterações contrácteis em 100% e hipocinesia inferior em 85,7%. Classe funcional I: 100% sem modificações ao seguimento. Escore de Rassi avaliado previamente ao evento foi de 4,85±0,89. Síncope constituiu a apresentação inicial em 100%, média de 2 episódios por paciente e intervalo de 4 semanas entre os mesmos. Houve alterações em 85,71% dos eletrocardiogramas, sendo bloqueio de ramo direito a principal. TV sustentada foi encontrada em 100%; sítio epicárdico em 71,42% e saída anterolateral do ventrículo esquerdo em 57,14%. A FVE sequencial foi de 54%±3,31; sem alterações contráteis novas. Amiodarona e betabloqueadores foram os fármacos utilizados. Terapias apropriadas aconteceram em 100%; média de 2,1 choques por paciente, com 52,63% dos registros nos primeiros 14 meses. Não foram evidenciados óbitos, terapias inapropriadas ou tempestade elétrica. Conclusão: O elevado número de terapias corrobora o risco arrítmico desta população, ratifica a importância do dispositivo e alerta para a eficácia da terapia clínica. Síncope pode estar associada a maior risco de eventos arrítmicos na CCC


Introduction: Chronic chagasic cardiopathy (CCC) encompasses a complex spectrum of presentations, and episodes of arrhythmic death in patients with preserved left ventricular (PLVF) or near normal (VFNN) are not uncommon. Methods: Retrospective evaluation of 7 patients with PLVF, submitted for implantation of implantable cardioverter defibrillator (ICD) due to tachycardia or ventricular fibrillation (VT / VF). Clinical, structural and electrocardiographic evaluations were performed. Results: Mean age was 57.5±4.45 years. Male sex comprised 71.4%. Left ventricular function (LVF) was 56.14%±4.45 with contractile changes in 100% and lower hypokinesia in 85.7%. Functional class I was evidenced in 100% without changes in follow-up. The Rassi score evaluated before the event was 4.85±0.89. Syncope was the initial presentation in 100%, average of 2 episodes per patient and interval of 4 weeks between them. Electrocardiogram showed alterations in 85.71% being right bundle branch block. Sustained VT was evidenced in 100%; epicardial site in 71.42% and left ventricular anterolateral outlet in 57.14%. The sequential LVF was 54%±3.31; without new contractile changes. Amiodarone and beta-blockers were the drugs used. Appropriate therapies occurred in 100%; average of 2.1 shocks per patient with 52.63% of the records in the first 14 months. There were no deaths, inappropriate therapies or electrical storm. Conclusion: The high number of therapies corroborates the arrhythmic risk of this population, ratifies the importance of the device and disputes the effectiveness of clinical therapy. Syncope may be associated with an increased risk of arrhythmic events in CCC


Assuntos
Humanos , Masculino , Feminino , Adulto , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/terapia , Função Ventricular , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Prevenção Secundária/métodos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Volume Sistólico , Síncope , Bloqueio de Ramo/complicações , Bloqueio de Ramo/diagnóstico , Ecocardiografia/métodos , Fatores Sexuais , Doença Crônica , Estudos Retrospectivos , Doença de Chagas/terapia , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico
7.
Braz J Cardiovasc Surg ; 33(1): 82-88, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617506

RESUMO

INTRODUCTION: Chagas disease represents an important health problem with socioeconomic impacts in many Latin-American countries. It is estimated that 20% to 30% of the people infected by Trypanosoma cruzi will develop chronic Chagas cardiomyopathy (CCC), which is generally accompanied by heart failure (HF). Cardiac resynchronization therapy (CRT) may be indicated for patients with HF and electromechanical dysfunctions. OBJECTIVE: The primary endpoint of this study was to analyze the response to CRT in patients with CCC, while the secondary endpoint was to estimate the survival rates of CRT responder patients. METHODS: This is an observational, cross-sectional and retrospective study. The records of 50 patients with CRT pacing devices implanted between June 2009 and March 2017 were analyzed. For statistical analyses, Pearson's correlation was used along with Student's t-test, and survival was analyzed using the Kaplan-Meier method. A P value of <0.05 was considered significant. RESULTS: Out of 50 patients, 56% were male, with a mean age of 63.4±13.3 years and an average CRT duration of 61.2±21.7 months. The mean QRS duration was 150.12±12.4 ms before and 116.04±2.2 ms after the therapy (P<0.001). The mean left ventricular ejection fractions (LVEF) were 29±7% and 39.1±12.2% before and after CRT, respectively (P<0.001). A total of 35 (70%) patients had a reduction of at least one New York Heart Association (NYHA) functional class after six months of therapy (P=0.014). The survival rate after 72 months was 45%. CONCLUSION: This study showed clinical improvement and a nonsignificant survival rate in patients with CCC after the use of CRT.


Assuntos
Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/terapia , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
8.
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
9.
Microbes Infect ; 20(3): 185-195, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29158000

RESUMO

We previously found that, in a mouse model of Chagas cardiomyopathy, 18% of the 9390 quantified unigenes were significantly regulated by Trypanosoma cruzi infection. However, treatment with bone marrow-derived mononuclear cells (MNCs) resulted in 84% transcriptomic recovery. We have applied new algorithms to reanalyze these datasets with respect to specific pathways [Chagas disease (CHAGAS), cardiac muscle contraction (CMC) and chemokine signaling (CCS)]. In addition to the levels of expression of individual genes we also calculated gene expression variability and coordination of expression of each gene with all others. These additional measures revealed changes in the control of transcript abundances and gene networking in CHAGAS and restoration following MNC treatment, not accessible using the conventional approach limited to the average expression levels. Moreover, our weighted pathway regulation analysis incorporated the contributions of all affected genes, eliminating the arbitrary cut-off criteria of fold-change and/or p-value for significantly regulated genes. The new analyses revealed that T. cruzi infection had large transcriptomic consequences for the CMC pathway and triggered a huge cytokine signaling. Remarkably, MNC therapy not only restored normal expression levels of numerous genes, but it also recovered most of the CHAGAS, CMC and CCS fabrics that were altered by the infection.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/terapia , Redes Reguladoras de Genes , Trypanosoma cruzi/fisiologia , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Transcriptoma/genética
10.
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
11.
Cytotherapy ; 19(11): 1339-1349, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28887011

RESUMO

In this review of cell therapies in Chagas disease, we cover aspects related to the disease, its treatment and world demographics, before proceeding to describe the preclinical and clinical trials performed using cell therapies in the search for an alternative therapy for the most severe and lethal form of this disease, chronic chagasic cardiomyopathy.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Doença de Chagas/terapia , Animais , Transplante de Medula Óssea/métodos , Cardiomiopatia Chagásica/terapia , Doença de Chagas/epidemiologia , Doença de Chagas/etiologia , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Transplante de Coração , Humanos , Camundongos
12.
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
13.
Infect Immun ; 85(9)2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28674032

RESUMO

Chagas disease, caused by infection with the protozoan parasite Trypanosoma cruzi, is a leading cause of heart disease ("chagasic cardiomyopathy") in Latin America, disproportionately affecting people in resource-poor areas. The efficacy of currently approved pharmaceutical treatments is limited mainly to acute infection, and there are no effective treatments for the chronic phase of the disease. Preclinical models of Chagas disease have demonstrated that antigen-specific CD8+ gamma interferon (IFN-γ)-positive T-cell responses are essential for reducing parasite burdens, increasing survival, and decreasing cardiac pathology in both the acute and chronic phases of Chagas disease. In the present study, we developed a genetically adjuvanted, dendritic cell-based immunotherapeutic for acute Chagas disease in an attempt to delay or prevent the cardiac complications that eventually result from chronic T. cruzi infection. Dendritic cells transduced with the adjuvant, an adenoviral vector encoding a dominant negative isoform of Src homology region 2 domain-containing tyrosine phosphatase 1 (SHP-1) along with the T. cruzi Tc24 antigen and trans-sialidase antigen 1 (TSA1), induced significant numbers of antigen-specific CD8+ IFN-γ-positive cells following injection into BALB/c mice. A vaccine platform transduced with the adenoviral vector and loaded in tandem with the recombinant protein reduced parasite burdens by 76% to >99% in comparison to a variety of different controls and significantly reduced cardiac pathology in a BALB/c mouse model of live Chagas disease. Although no statistical differences in overall survival rates among cohorts were observed, the data suggest that immunotherapeutic strategies for the treatment of acute Chagas disease are feasible and that this approach may warrant further study.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Cardiomiopatia Chagásica/terapia , Imunoterapia/métodos , Vacinas/imunologia , Adenoviridae/genética , Animais , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Cardiomiopatia Chagásica/prevenção & controle , Células Dendríticas/imunologia , Modelos Animais de Doenças , Portadores de Fármacos , Feminino , Vetores Genéticos , Interferon gama/metabolismo , Camundongos Endogâmicos BALB C , Análise de Sobrevida , Transdução Genética , Resultado do Tratamento , Vacinas/administração & dosagem , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
14.
Arq Bras Cardiol ; 108(6): 546-551, 2017 Jun.
Artigo em Inglês, Português | MEDLINE | ID: mdl-28699977

RESUMO

Background:: Chagas disease continues to be a serious public health problem, and accounts for 25-30% of the indications for cardiac stimulation in Brazil. Objective:: To assess clinical and epidemiological characteristics of patients with Chagas disease, younger than 18 years, who had undergone pacemaker implantation in Brazil between 1994 and 2011, and its temporal trend. Methods:: This was a cross-sectional analysis of data from the Brazilian Pacemaker Registry database. The following variables were analyzed: year when pacemaker was implanted, location, age, sex, ethnic group, functional class and the main electrocardiographic findings at baseline. Results:: In a total of 183,123 implants performed between 1994 and 2011, 214 implants of cardiac stimulation device in Chagas disease patients aged younger than 18 years were identified. Mean age at implantation was 5.6 ± 6.2 years. Second- and third-degree atrioventricular blocks corresponded to 71% of indications for pacemaker implantation. Fifty-six percent of the procedures were performed in the southeast region. Regarding the total number of pacemaker implants per year, there was a remarkable increase in the implants for all causes. However, time series analysis of the implants in Chagas disease patients younger than 18 years revealed a significant reduction in the annual number of implants. Conclusion:: There has been an important reduction in the number of pacemaker implantations among children and adolescents with Chagas disease, suggesting a reduction in the vertical transmission of the parasite. Fundamento:: A doença de Chagas mantém-se como sério problema de saúde pública e tem sido responsável por aproximadamente 25% a 30% das indicações de estimulação cardíaca no Brasil. Objetivo:: Estudar as características clínicas e epidemiológicas dos pacientes menores de 18 anos portadores de doença de Chagas submetidos a implante de marca-passo no território brasileiro entre 1994 e 2011, e sua tendência temporal. Métodos:: Trata-se de um estudo retrospectivo que utilizou informações coletadas pelo Registro Brasileiro de Marca-passo. As variáveis analisadas foram: ano do implante, localidade, idade, sexo, grupo étnico dos pacientes; classificação funcional e os principais achados eletrocardiográficos de base. Resultados:: Em um total de 183 123 implantes realizados entre 1994 e 2011, foram identificados 214 implantes de dispositivos de estimulação cardíaca em portadores de doença de Chagas com idade inferior a 18 anos. A média de idade no momento do implante foi de 5,6 ± 6,2 anos. Bloqueios atrioventriculares de 2º e 3º graus foram responsáveis por 71% das indicações. Dos procedimentos, 55,6% foram realizados na região sudeste. Em relação ao total de implantes de marca-passo por ano, observamos um aumento importante e significante de implante por todas as causas. Entretanto, quando avaliamos a série temporal de implantes em pacientes com doença de Chagas menores que 18 anos, observamos uma redução expressiva e significativa no número anual de implantes. Conclusão:: Observa-se uma redução importante do número de implantes de marca-passo em crianças e adolescente chagásicos, o que sugere uma redução da transmissão vertical do parasita.


Assuntos
Cardiomiopatia Chagásica/terapia , Marca-Passo Artificial , Adolescente , Brasil/epidemiologia , Cardiomiopatia Chagásica/epidemiologia , Criança , Estudos Transversais , Humanos , Incidência , Marca-Passo Artificial/estatística & dados numéricos , Fatores Socioeconômicos , Resultado do Tratamento
15.
Heart ; 103(9): 651-658, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28285268

RESUMO

The heart may be affected directly or indirectly by a variety of protozoa and helminths. This involvement may manifest in different ways, but the syndromes resulting from impairment of the myocardium and pericardium are the most frequent. The myocardium may be invaded by parasites that trigger local inflammatory response with subsequent myocarditis or cardiomyopathy, as occurs in Chagas disease, African trypanosomiasis, toxoplasmosis, trichinellosis and infection with free-living amoebae. In amoebiasis and echinococcosis, the pericardium is the structure most frequently involved with consequent pericardial effusion, acute pericarditis, cardiac tamponade or constrictive pericarditis. Chronic hypereosinophilia due to helminth infections, especially filarial infections, has been associated with the development of tropical endomyocardial fibrosis, a severe form of restrictive cardiomyopathy. Schistosomiasis-associated lung vasculature involvement may cause pulmonary hypertension (PH) and cor pulmonale Tropical pulmonary eosinophilia, which is characterised by progressive interstitial fibrosis and restrictive lung disease, may lead to PH and its consequences may occur in the course of filarial infections. Intracardiac rupture of an Echinococcus cyst can cause membrane or secondary cysts embolisation to the lungs or organs supplied by the systemic circulation. Although unusual causes of cardiac disease outside the endemic areas, heart involvement by parasites should be considered in the differential diagnosis especially of myocardial and/or pericardial diseases of unknown aetiology in both immunocompetent and immunocompromised individuals. In this review, we updated and summarised the current knowledge on the major heart diseases caused by protozoan and metazoan parasites, which either involve the heart directly or otherwise influence the heart adversely.


Assuntos
Cardiopatias/parasitologia , Coração/parasitologia , Leishmaniose/parasitologia , Esquistossomose/parasitologia , Tripanossomíase Africana/parasitologia , Biópsia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Diagnóstico Diferencial , Ecocardiografia , Fibrose Endomiocárdica/diagnóstico , Fibrose Endomiocárdica/parasitologia , Fibrose Endomiocárdica/fisiopatologia , Fibrose Endomiocárdica/terapia , Coração/fisiopatologia , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Interações Hospedeiro-Parasita , Humanos , Leishmaniose/diagnóstico , Leishmaniose/fisiopatologia , Leishmaniose/terapia , Valor Preditivo dos Testes , Prognóstico , Esquistossomose/diagnóstico , Esquistossomose/fisiopatologia , Esquistossomose/terapia , Tripanossomíase Africana/diagnóstico , Tripanossomíase Africana/fisiopatologia , Tripanossomíase Africana/terapia
16.
Rev Assoc Med Bras (1992) ; 63(1): 57-63, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28225875

RESUMO

OBJECTIVE: To evaluate clinical and epidemiological characteristics and clinical outcomes in patients hospitalized with decompensated heart failure (DHF), with a comparison between Chagas and non-Chagas disease. METHOD: This is a retrospective cohort study involving 136 patients consecutively admitted with DHF between January 1 and December 31, 2011, with the following outcomes: acute renal failure, cardiogenic shock, rehospitalization, and hospital death. Individuals aged ≥ 18 years with DHF were included while those with more than 10% of missing data regarding outcomes were excluded. Statistical analysis was performed using SPSS version 17.0. Chi-squared test was used to compare proportions. Student's T test was used to compare means. Kaplan-Meier and log-rank tests were used to compare rehospitalization rates between the two groups over time. RESULTS: Chagasic and non-chagasic patients were compared. The first had lower mean systolic blood pressure (111.8±18.4 versus 128.8±24.4, p<0.01), lower mean diastolic blood pressure (74.5±13.6 versus 82.0±15.2, p<0.01) and lower left ventricular ejection fraction (26.5±6.2 versus 41.5±18.9, p<0.01). In all, 20 patients with Chagas (50.1%) were rehospitalized, compared to 35 patients in the non-Chagas group (35.4%, p=0.04). Log rank test = 4.5 (p<0.01) showed that rehospitalization rates between the two groups over time (Kaplan-Meier curves) differed. CONCLUSION: Chagas disease was associated with lower systolic and diastolic blood pressure and lower left ventricular ejection fraction. The rehospitalization rate was higher in Chagas disease.


Assuntos
Cardiomiopatia Chagásica , Insuficiência Cardíaca , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Cardiomiopatia Chagásica/epidemiologia , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Estudos de Coortes , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Fatores Socioeconômicos , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
17.
Cardiol Clin ; 35(1): 31-47, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27886788

RESUMO

The initial infection of Chagas disease is typically asymptomatic, but approximately 30% of people will progress to a chronic cardiac form, and others develop the gastrointestinal form. Death is often sudden due to arrhythmias or progressive heart failure. Prevention through vector control programs and blood bank screening, along with strengthened surveillance systems and rapid information sharing, are key to decreasing disease burden globally. The epidemiology, diagnostic evaluation, diagnosis, and treatment of acute and chronic Chagas cardiac disease are discussed with focus on educating the primary care professionals and general cardiologists in nonendemic areas who have limited experience treating this disease.


Assuntos
Cardiomiopatia Chagásica , Gerenciamento Clínico , Américas/epidemiologia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/epidemiologia , Cardiomiopatia Chagásica/terapia , Humanos , Morbidade/tendências
18.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 26(4): 246-52, out.-dez.2016.
Artigo em Português | LILACS | ID: biblio-831559

RESUMO

O diagnóstico de cardiomiopatia chagásica crônica deve ser considerado em todo paciente proveniente de áreas endêmicas, que apresente história de doença cardíaca e anormalidades no exame cardiológico, na vigência de duas reações sorológicas positivas (ELISA, imunofluorescência indireta ou hemaglutinação indireta). O ECG convencional e o ecocardiograma transtorácico são fundamentais para revelar a presença de cardiomiopatia subjacente. O tratamento da cardiomiopatia da doença de Chagas deve contemplar as diferentes formas de apresentação da moléstia ­ dor precordial, tromboembolismo, arritmias cardíacas, morte súbita e insuficiência cardíaca crônica (ICC). A dor precordial deve ser tratada com betabloqueadores, antagonistas do cálcio ou nitratos. O tratamento do tromboembolismo deve ser oferecido para os pacientes com alto risco de desenvolver o fenômeno, ou seja, que apresentam fibrilação atrial, trombose mural, tromboembolismo prévio e aqueles com o aneurisma de ponta do VE. Pacientes com taquicardia ventricular sustentada e aqueles recuperados de morte súbita devem receber implante de desfibrilador-cardioversor para a prevenção secundária de morte súbita cardíaca. O tratamento da ICC deve ser semelhante ao preconizado para a ICC de etiologia não chagásica, visto que a fisiopatologia é semelhante, contemplando-se o uso de mineralocorticoides, betabloqueadores, antagonistas da enzima conversora de angiotensinogênio em angiotensina e diuréticos. A digoxina deve ser usada com cautela nesses pacientes, preferencialmente com monitoração de níveis séricos. A terapia de ressincronização cardíaca parece ser promissora nos pacientes com tratamento medicamentoso otimizado. Na ICC terminal, o transplante cardíaco é opção terapêutica segura, tendo em vista os resultados, no mínimo, semelhantes aos observados em pacientes não chagásicos


The diagnosis of chronic Chagas cardiomyopathy should be considered in all patients from endemic areas, presenting history of heart disease and abnormalities in the cardiac examination, in the presence of two positive serologic reactions (ELISA, indirect immunofluorescence, or indirect hemagglutination). The conventional ECG and the transthoracic echocardiography are crucial to reveal the presence of underlying cardiomyopathy. The treatment of Chagas cardiomyopathy should address the different forms of the disease ­ precordial chest pain, thromboembolism, cardiac arrhythmias, sudden death, and chronic heart failure (CHF). Precordial chest pain should be treated with beta-blockers, calcium antagonists, or nitrates. The treatment of thromboembolism should be given to patients at high risk of developing the condition, i.e., that have atrial fibrillation, mural thrombosis, previous thromboembolism, and left ventricular apical aneurysm. Patients with sustained ventricular tachycardia and those with previous cardiac arrest should receive implantable cardioverter-defibrillator for secondary prevention of sudden cardiac death. The treatment of CHF is similar to that recommended to non-Chagas disease heart failure, inasmuch as the pathophysiology is similar, consisting of mineralocorticoids, beta-blockers, angiotensin converting enzyme inhibitors, and diuretics. Digoxin should be used with caution in such patients, preferentially with monitoring of serum levels. Cardiac resynchronization therapy seems promising in patients on optimized medical therapy. In end-stage CHF, heart transplantation is a safe therapeutic option, as the results are at least similar to those found in non-Chagas disease patients


Assuntos
Humanos , Masculino , Feminino , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/terapia , Doença de Chagas/etiologia , Insuficiência Cardíaca/etiologia , Transplante de Coração/reabilitação , Doença Crônica/epidemiologia , Morte Súbita , Ecocardiografia Doppler , Eletrocardiografia , Furosemida/administração & dosagem , Espironolactona/administração & dosagem , Tromboembolia/diagnóstico
19.
Arq Bras Cardiol ; 107(2): 99-100, 2016 Aug.
Artigo em Inglês, Português | MEDLINE | ID: mdl-27411097

RESUMO

BACKGROUND: The outcome of Chagas disease patients after receiving implantable cardioverter defibrillator (ICD) is still controversial. OBJECTIVE: To compare clinical outcomes after ICD implantation in patients with chronic Chagas cardiomyopathy (CCC) and ischemic heart disease (IHD). METHODS: Prospective study of a population of 153 patients receiving ICD (65 with CCC and 88 with IHD). The devices were implanted between 2003 and 2011. Survival rates and event-free survival were compared. RESULTS: The groups were similar regarding sex, functional class and ejection fraction. Ischemic patients were, on average, 10 years older than CCC patients (p < 0.05). Patients with CCC had lower schooling and monthly income than IHD patients (p < 0.05). The number of appropriate therapies was 2.07 higher in CCC patients, who had a greater incidence of appropriate shock (p < 0.05). Annual mortality rate and electrical storm incidence were similar in both groups. There was no sudden death in CCC patients, and only one in IHD patients. Neither survival time (p = 0.720) nor event-free survival (p = 0.143) significantly differed between the groups. CONCLUSION: CCC doubles the risk of receiving appropriate therapies as compared to IHD, showing the greater complexity of arrhythmias in Chagas patients.


Assuntos
Cardiomiopatia Chagásica/terapia , Desfibriladores Implantáveis/estatística & dados numéricos , Isquemia Miocárdica/terapia , Adulto , Idoso , Cardiomiopatia Chagásica/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Life Sci ; 152: 210-9, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27040670

RESUMO

AIMS: The rational basis that explains the benefits of exercise therapy on Chagas cardiomyopathy (ChC) is poorly understood. This study investigated the impact of an exercise program on exercise performance, heart parasitism, immunoinflammatory response, fibrogenesis, oxidative damage, and cardiomyocytes contractility in experimental ChC. MAIN METHODS: Wistar rats were subjected to a 9-week treadmill running training and challenged with Trypanosoma cruzi. Control animals remained sedentary. Physical and metabolic performance, cardiac morphology, cytokines, chemokines, nitric oxide, oxidative tissue damage, cardiomyocyte morphology and contractility were analyzed. KEY FINDINGS: Exercise training was efficient to improve physical performance and anaerobic threshold in trained animals. By increasing cardiac and serum levels of cytokines (TNF-α, IFN-γ, and IL-6), chemokines (MCP-1 and CX3CL1), the myocardial activity catalase and superoxide dismutase, and reducing lipid and protein oxidation in cardiac tissue, exercise training seem to be a beneficial strategy to mitigate the progression and severity of Chagas-associated cardiomyopathy. SIGNIFICANCE: The protective adaptations to the host triggered by exercise training contributed to reduce cardiac parasitism, inflammation, fibrosis and cardiomyocytes atrophy. Although exercise training does not affect nitric oxide levels in cardiac tissue from infected animals, this strategy enhanced the efficiency of endogenous antioxidant mechanisms, restricting oxidative tissue damage with positive repercussions to cardiomyocytes biomechanics in rats.


Assuntos
Antioxidantes/metabolismo , Cardiomiopatia Chagásica/metabolismo , Cardiomiopatia Chagásica/terapia , Terapia por Exercício/métodos , Inflamação/patologia , Limiar Anaeróbio , Animais , Cardiomiopatia Chagásica/patologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Miocárdio/patologia , Miócitos Cardíacos/patologia , Parasitemia/sangue , Parasitemia/parasitologia , Ratos , Ratos Wistar , Comportamento Sedentário , Trypanosoma cruzi , Remodelação Ventricular
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