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2.
Am J Cardiol ; 125(9): 1413-1420, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171439

RESUMO

Chagas heart disease (HD) is a chronic fibrosing myocarditis with high mortality. The PEACH study aimed to evaluate if exercise training can improve the functional capacity of Chagas HD patients with left ventricular dysfunction and/or heart failure. The PEACH study was a single center, parallel-group, clinical trial that randomized 30 clinical stable Chagas HD patients with left ventricular ejection fraction <45% or heart failure symptoms to either supervised exercise training 3 times/week for 6 months or a control group. Both groups had the same monthly pharmaceutical and nutritional counseling and usual care. Primary end point was functional capacity assessed by peak exercise oxygen consumption (peak VO2) obtained by cardiopulmonary exercise test. Secondary end points included other cardiopulmonary exercise test variables, cardiac function by echocardiography, body composition, muscle respiratory strength, and metabolic biomarkers. Peak VO2 increased among patients in exercise group from 17.60 ± 4.65 mlO2 kg-1 min-1 to 19.40 ± 5.51 mlO2 kg-1 min-1 while decreased in controls from 15.40 ± 6.30 mlO2 kg-1 min-1 to 12.96 ± 4.50 mlO2 kg-1 min-1, resulting in significant difference in change in peak VO2 between groups after 6 months (ß = +4.6, p = 0.004). There were significant differences between groups in changes in anaerobic threshold (ß = 3.7, p = 0.05), peak oxygen pulse (ß = +2.7, p = 0.032) and maximum minute ventilation (ß = +13.9, p < 0.0001) after 6 months of intervention. In conclusion, exercise training improved functional capacity of chronic Chagas HD patients with left ventricular dysfunction and/or heart failure.


Assuntos
Cardiomiopatia Chagásica/terapia , Exercício Físico , Idoso , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/fisiopatologia , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
3.
Rev Assoc Med Bras (1992) ; 65(11): 1391-1396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31800902

RESUMO

BACKGROUND: Cardiac resynchronization therapy (CRT) is a therapeutic modality for patients with heart failure (HF). The effectiveness of this treatment for event reduction is based on clinical trials where the population of patients with Chagas' disease (DC) is underrepresented. OBJECTIVE: To evaluate the prognosis after CRT of a population in which CD is an endemic cause of HF. METHODS: A retrospective cohort conducted between January 2015 and December 2016 that included patients with HF and left ventricular ejection fraction (LVEF) of less than 35% and undergoing CRT. Clinical and demographic data were collected to search for predictors for the combined outcome of death or hospitalization for HF at one year after CRT implantation. RESULTS: Fifty-four patients were evaluated, and 13 (24.1%) presented CD as the etiology of HF. The mean LVEF was 26.2± 6.1%, and 36 (66.7%) patients presented functional class III or IV HF. After the mean follow-up of 15 (±6,9) months, 17 (32.1%) patients presented the combined outcome. In the univariate analysis, CD was associated with the combined event when compared to other etiologies of HF, 8 (47%) vs. 9 (13,5%), RR: 3,91 CI: 1,46-10,45, p=0,007, as well as lower values of LVEF. In the multivariate analysis, CD and LVEF remained independent risk factors for the combined outcome. CONCLUSION: In a population of HF patients undergoing CRT, CD was independently associated with mortality and hospitalization for HF.


Assuntos
Terapia de Ressincronização Cardíaca , Cardiomiopatia Chagásica/terapia , Insuficiência Cardíaca/terapia , Idoso , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/mortalidade , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/parasitologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas , Falha de Tratamento
4.
JACC Clin Electrophysiol ; 5(10): 1213-1223, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31648747

RESUMO

OBJECTIVES: The goal of this analysis was to pool data from published studies on outcomes after implantable cardioverter-defibrillator (ICD) therapy in patients with Chagas heart disease (CHD). BACKGROUND: CHD is characterized by a high burden of ventricular arrhythmias and an increased risk of sudden cardiac death. The indications for ICD are not well established. METHODS: An extensive literature search without language restrictions was performed to identify all studies on ICD therapy in patients with CHD. A random effects model was used to calculate percentages and 95% confidence intervals (CIs). RESULTS: Of 397 articles screened, 13 studies (all observational) were included. There were 1,041 patients (mean age at implantation 57 ± 11 years; 64% men), most of whom (92%) received an ICD for secondary prevention. Antiarrhythmic medication consisted of amiodarone (79%) and beta-blockers (44%). Overall, the annual all-cause mortality rate was 9.0% (95% CI: 6.9 to 11.7) in 2.8 ± 1.9 years of follow-up, and the annual sudden cardiac death rate was 2.0% (95% CI: 1.3 to 3.3) in 2.6 ± 1.9 years. In addition, 24.8% (95% CI: 15.7 to 37.0) of patients received 1 or more appropriate interventions (shocks or antitachycardia pacing), 4.7% (95% CI: 3.2 to 6.9) received inappropriate shocks, and 9.1% (95% CI: 5.5 to 14.7) had electric storms annually. CONCLUSIONS: In patients with an ICD, annual all-cause mortality rate was 9%. Appropriate ICD interventions and electric storms were frequent, occurring at a rate of 25% and 9% per year, respectively. Inappropriate ICD shocks were not infrequent (5% per year). The benefits and risks of ICD therapy in patients with CHD should be carefully weighed until data from better studies become available.


Assuntos
Cardiomiopatia Chagásica/terapia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Morte Súbita Cardíaca/epidemiologia , Cardioversão Elétrica , Humanos , Prevenção Primária , Prevenção Secundária , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiologia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/epidemiologia
5.
J Cardiovasc Electrophysiol ; 30(11): 2448-2452, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31502385

RESUMO

INTRODUCTION: There are conflicting data regarding the efficacy of implantable cardioverter-defibrillator (ICD) in Chagas disease (CD) patients. This study aims to evaluate the short-term outcome after ICD for secondary prevention, in a population where CD is a prevalent cause of heart failure (HF). METHODS AND RESULTS: Consecutive patients with HF and reduced left ventricular ejection fraction (LVEF), who underwent ICD implantation for secondary prevention of SCD. Clinical and demographic data were collected to investigate mortality predictors at 1 year. During the study period, 117 patients underwent ICD implantation, of which 108 were included. The most frequent causes of HF was CD: 52 (48.1%) and ischemic cardiomyopathy: 20 (18.5%). Chagas and non-Chagas patients were well balanced-male: 32 (61.5%) vs 38 (67.9%), P = .548; age: 59.2 (±10.9) vs 56.8 (±13.4), P = .681; and LVEF: 34.1 (±0.2) vs 31.3 (±8.7), P = .064, respectively. At the mean follow-up of 15.7 months, overall mortality occurred in 14 (12.9%) patients, with a higher incidence in patients with CD cardiomyopathy, 11 (21.2%) vs 3 (5.4%), P = .021 (log-rank). In the multivariate analysis, CD remained as an independent predictor for death (hazard ratio: 4.62, confidence interval [95% CI]: 1.27-16.81, P = .021). CONCLUSION: CD was associated with a poor short-term outcome in patients with HF submitted to ICD implantation for secondary prevention when compared with other HF etiologies. In this specific HF population, ICD indication should be individualized, considering the worst prognosis of these patients.


Assuntos
Cardiomiopatia Chagásica/terapia , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Insuficiência Cardíaca/terapia , Prevenção Secundária/instrumentação , Adulto , Idoso , Brasil/epidemiologia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
6.
Stem Cell Reports ; 12(6): 1232-1241, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31105048

RESUMO

Chagas disease (ChD) is one of the most neglected tropical diseases, with cardiomyopathy being the main cause of death in Trypanosoma cruzi-infected patients. As the parasite actively replicates in cardiomyocytes (CMs), the heart remains a key target organ in the pathogenesis of ChD. Here we modeled ChD using human induced pluripotent stem cell-derived CMs (iPSC-CMs) to understand the complex interplay between the parasite and host cells. We showed that iPSC-CMs can get infected with the T. cruzi Y strain and that all parasite cycle stages can be identified in our model system. Importantly, characterization of T. cruzi-infected iPSC-CMs showed significant changes in their gene expression profile, cell contractility, and distribution of key cardiac markers. Moreover, these infected iPSC-CMs exhibited a pro-inflammatory profile as indicated by significantly elevated cytokine levels and cell-trafficking regulators. We believe our iPSC-CM model is a valuable platform to explore new treatment strategies for ChD.


Assuntos
Cardiomiopatia Chagásica/metabolismo , Células-Tronco Pluripotentes Induzidas , Modelos Biológicos , Miócitos Cardíacos , Trypanosoma cruzi/metabolismo , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/terapia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/parasitologia , Células-Tronco Pluripotentes Induzidas/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/parasitologia , Miócitos Cardíacos/patologia
7.
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
8.
Europace ; 21(7): 1070-1078, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30820579

RESUMO

AIMS: Data on long-term follow-up of patients with Chagas' heart disease (ChHD) receiving a secondary prevention implantable cardioverter-defibrillator (ICD) are limited and its benefit is controversial. The aim of this study was to evaluate the long-term outcomes of ChHD patients who received a secondary prevention ICD. METHODS AND RESULTS: We assessed the outcomes of consecutive ChHD patients referred to our Institution from 2006 to 2014 for a secondary prevention ICD [89 patients; 58 men; mean age 56 ± 11 years; left ventricular ejection fraction (LVEF), 42 ± 12%]. The primary outcome included a composite of death from any cause or heart transplantation. After a mean follow-up of 59 ± 27 months, the primary outcome occurred in 23 patients (5.3% per year). Multivariate analysis showed that LVEF < 35% [hazard ratio (HR) 4.64; P < 0.01] and age ≥ 65 years (HR 3.19; P < 0.01) were independent predictors of the primary outcome. Using these two risk factors, a risk score was developed, and lower- (no risk factors), intermediate- (one risk factor), and higher-risk (two risk factors) groups were recognized with an annual rate of primary outcome of 1.4%, 7.4%, and 20.4%, respectively. A high burden of appropriate ICD therapies (16% per year) and electrical storms were documented, however, ICD interventions did not impact on the primary outcome. CONCLUSION: Among ChHD patients receiving a secondary prevention ICD, older age (≥65 years) and left ventricular dysfunction (LVEF < 35%) portend a poor outcome and were associated with increased risk of death or heart transplantation. Most patients received appropriate ICD therapies, however, ICD interventions did not impact on the primary outcome.


Assuntos
Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/terapia , Desfibriladores Implantáveis , Transplante de Coração , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/terapia , Idoso , Feminino , Seguimentos , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Prevenção Secundária , Volume Sistólico
9.
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
10.
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
11.
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
12.
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
14.
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
15.
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
16.
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
17.
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
18.
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.
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
20.
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
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