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2.
Arq. bras. cardiol ; Arq. bras. cardiol;119(1): 3-11, abr. 2022. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1383729

RESUMO

Resumo Fundamento: Na cardiomiopatia chagásica crônica (CCC), impõem-se estudos com a proposta de identificar fatores de risco arritmogênicos em pacientes nos quais a disfunção ventricular de moderada a grave não está presente. Objetivos: Verificar a dependência entre arritmias ventriculares frequentes (ARV), fração de ejeção de ventrículo esquerdo (FEVE), extensão da fibrose pela ressonância magnética cardíaca (RMC) e dosagem de norepinefrina urinária (NOREPI) na CCC com FEVE preservada ou minimamente comprometida. Métodos: Foi analisada no Holter a presença de extrassístoles ventriculares >30/hora. Na RMC, avaliou-se a FEVE e a quantificação de massa fibrosada. Foi realizada a dosagem de NOREPI pelo método de Muskiet. A matriz de correlação foi calculada para aferir a capacidade de as variáveis preverem outra sendo considerado significante p<0,05. Resultados: Foram incluídos no estudo 59 pacientes, com idade média de 57,9±10,94 anos. Arritmia ventricular frequente (ARV) foi detectada em 28 pacientes. A variável fibrose mostrou-se inversamente proporcional à fração de ejeção de ventrículo esquerdo (FEVE) (R de −0,61) e à norepinefrina urinária (NOREPI) (R de −0,68), assim como a variável ARV mostrou-se inversamente proporcional à FEVE (R de −0,33) e à NOREPI (R de −0,27). Já a FEVE mostrou-se diretamente proporcional à NOREPI (R de 0,83). Conclusão: Nesta amostra, em pacientes com CCC com FEVE preservada ou discretamente reduzida, observa-se a integridade do sistema nervoso autonômico em corações com pouca fibrose e FEVE mais elevada, apesar da presença de tradicionais fatores de risco para morte súbita cardíaca. Há dependência entre os níveis de NOREPI, FEVE e fibrose miocárdica, mas não com ARV.


Abstract Background: In Chronic Chagas Cardiomyopathy (CCC), studies are needed to identify arrhythmogenic risk factors in patients in which moderate to severe ventricular dysfunction is not present. Objective: To verify the correlation between frequent ventricular arrhythmias (PVC), left ventricular ejection fraction (LVEF), extension of fibrosis by cardiac magnetic resonance (CMR), and urinary norepinephrine measurement (NOREPI) in CCC with preserved or mildly compromised LVEF. Methods: The presence of ventricular extrasystoles > 30/h was analyzed on Holter. At CMR, LVEF and quantification of fibrosis mass were evaluated. The dosage of NOREPI was performed using the Muskiet method. The correlation coefficient matrix was calculated to measure the predictive ability of the variables to predict another variable, with p < 0.05 being considered significant. Results: A total of 59 patients were included. The mean age was 57.9 + 10.94 years. PVC was detected in 28 patients. The fibrosis variable was inversely proportional to LVEF (R of −0.61) and NOREPI (R of −0.68). Also, the variable PVC was inversely proportional to LVEF (R of −0.33) and NOREPI (R of −0.27). On the other hand, LVEF was directly proportional to NOREPI (R of 0.83). Conclusion: In this sample, in patients with CCC with preserved or slightly reduced LVEF, integrity of the autonomic nervous system is observed in hearts with little fibrosis and higher LVEF despite the presence of traditional risk factors for sudden cardiac death. There is correlation between the levels of NOREPI, LVEF, and myocardial fibrosis, but not with PVC.

3.
Mem. Inst. Oswaldo Cruz ; 117: e220019, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1365154

RESUMO

Chagas disease (CD), caused by infection by the protozoan parasite Trypanosoma cruzi, presents as main clinical manifestation the chronic chagasic cardiomyopathy (CCC). CCC afflicts millions of people, mostly in Latin America, and vaccine and effective therapy are still lacking. Comprehension of the host/parasite interplay in the chronic phase of T. cruzi infection may unveil targets for rational trait-based therapies to improve CCC prognosis. In the present viewpoint, I critically summarise a collection of data, obtained by our network of collaborators and other groups on CCC and preclinical studies on pathogenesis, targeting identification for intervention and the use of drugs with immunomodulatory properties to improve CCC. In the last two decades, models combining mouse lineages and T. cruzi strains allowed replication of crucial clinical, histopathological, and immunological traits of CCC. This condition includes conduction changes (heart rate changes, arrhythmias, atrioventricular blocks, prolongation of the QRS complex and PR and corrected QT intervals), ventricular dysfunction and heart failure, CD8-enriched myocarditis, tissue remodeling and progressive fibrosis, and systemic inflammatory profile, resembling "cytokine storm". Studies on Chagas' heart disease pathogenesis begins to unveil the molecular mechanisms underpinning the inflammation-related cardiac tissue damage, placing IFNγ, TNF and NFκB signaling as upstream regulators of miRNAs and mRNAs associated with critical biological pathways as cell migration, inflammation, tissue remodeling and fibrosis, and mitochondrial dysfunction. Further, data on preclinical trials using hypothesis-based tools, targeting parasite and inflammation-related alterations, opened paths for multi-therapeutic approaches in CCC. Despite the long path taken using experimental CD models replicating relevant aspects of CCC and testing new therapies and therapeutic schemes, these findings may get lost in translation, as conceptual and economical challenges, underpinning the valley of death across preclinical and clinical trials. It is hoped that such difficulties will be overcome in the near future.

5.
FASEB J ; 35(10): e21901, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34569665

RESUMO

Chagasic cardiomyopathy (CCC) is one of the main causes of heart failure and sudden death in Latin America. To date, there is no available medication to prevent or reverse the onset of cardiac symptoms. CCC occurs in a scenario of disrupted calcium dynamics and enhanced oxidative stress, which combined, may favor the hyper activation of calcium/calmodulin (Ca2+ /CaM)-calcium/calmodulin-dependent protein kinase II (CaMKII) (Ca2+ /CaM-CaMKII) pathway, which is fundamental for heart physiology and it is implicated in other cardiac diseases. Here, we evaluated the association between Ca2+ /CaM-CaMKII in the electro-mechanical (dys)function of the heart in the early stage of chronic experimental Trypanosoma cruzi infection. We observed that in vitro and ex vivo inhibition of Ca2+ /CaM-CaMKII reversed the arrhythmic profile of isolated hearts and isolated left-ventricles cardiomyocytes. The benefits of the limited Ca2+ /CaM-CaMKII activation to cardiomyocytes' electrical properties are partially related to the restoration of Ca2+ dynamics in a damaged cellular environment created after T. cruzi infection. Moreover, Ca2+ /CaM-CaMKII inhibition prevented the onset of arrhythmic contractions on isolated heart preparations of chagasic mice and restored the responsiveness to the increase in the left-ventricle pre-load. Taken together, our data provide the first experimental evidence for the potential of targeting Ca2+ /CaM-CaMKII pathway as a novel therapeutic target to treat CCC.


Assuntos
Arritmias Cardíacas/metabolismo , Sinalização do Cálcio , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Calmodulina/metabolismo , Cardiomiopatia Chagásica/metabolismo , Trypanosoma cruzi/metabolismo , Animais , Arritmias Cardíacas/parasitologia , Cardiomiopatia Chagásica/parasitologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos BALB C
6.
Rev. Pesqui. Fisioter ; 11(1): 85-95, Fev. 2021. ilus, tab
Artigo em Inglês, Português | LILACS | ID: biblio-1252906

RESUMO

INTRODUÇÃO: A doença de Chagas (DC) constitui uma infecção parasitária causada pelo protozoário flagelado Tripanosoma cruzi. Estimativas apontam a existência de, aproximadamente, cinco milhões de indivíduos infectados, principalmente na América Latina, com o Brasil datando entre 1,9 a 4,6 milhões de indivíduos sob o mesmo aspecto infeccioso. O desfecho cardíaco configura um dos aspectos mais importantes, com manifestações condizentes à disfunção ventricular sistólica ou diastólica, disfunção autonômica cardíaca e morte súbita. OBJETIVO: correlacionar o estilo de vida e o nível de atividade física de indivíduos portadores de miocardiopatia chagásica (MC). MATERIAL E MÉTODOS: Realizou-se um estudo analítico, de corte transversal, em ambulatório de referência para Miocardiopatias, com abrangência estadual. Utilizou-se formulário próprio construído pelas autoras, o qual contemplava além das variáveis clínicas e demográficas, variáveis relativas à análise do estilo de vida e atividade física dos participantes, sendo esse aplicado em sala de espera, enquanto os sujeitos aguardavam atendimento médico. RESULTADOS: Foram selecionados 74 indivíduos portadores de MC. A média de idade da amostra foi de 61,2 ± 8,5 anos, sendo que 50 (68,0%) indivíduos eram do sexo feminino. Em relação ao nível de atividade física, houve predomínio da categoria "não ativo", correspondendo a 60 indivíduos (71,0%). O estilo de vida foi classificado como "muito bom" para 41 (55,0%) participantes e "bom" para 22 (30,0%) participantes, não havendo indivíduos alocados na categoria "necessita melhorar" do questionário. CONCLUSÃO: Os resultados obtidos permitem concluir que, de modo geral, o estilo de vida e o nível de atividade física de indivíduos portadores de MC caracterizaram-se como "bom" / "muito bom" e não ativos, respectivamente.


INTRODUCTION: Chagas disease (CD) is a parasitic infection caused by the flagellated protozoan Trypanosoma cruzi. Estimates point to the existence of approximately five million infected individuals, mainly in Latin America, with Brazil dating between 1.9 and 4.6 million individuals under the same infectious aspect. The cardiac outcome is one of the most important aspects with manifestations consistent with systolic or diastolic ventricular dysfunction, cardiac autonomic dysfunction, and sudden death. OBJECTIVE: To correlate the lifestyle and physical activity level of individuals with Chagas cardiomyopathy (CM). MATERIAL AND METHODS: A cross-sectional analytical study was carried out in a reference outpatient clinic for cardiomyopathies, with state coverage. A form was created by the authors, which included, in addition to the clinical variables and demographic, variables related to the analysis of the participants' lifestyle and physical activity, this being applied in the waiting room, while the subjects waited for medical care. RESULTS: Seventy-four individuals with CM were selected. The mean age of the sample was 61.2 ± 8.5 years, with 50 (68.0%) individuals being female. Regarding the level of physical activity, the "not active" category was predominant, corresponding to 60 individuals (71.0%). The lifestyle was classified as "very good" for 41 (55.0%) participants and "good" for 22 (30.0%) participants, with no individuals allocated to the "need to improve" category of the questionnaire. CONCLUSION: The results obtained allow us to conclude that, in general, the lifestyle and the level of physical activity of individuals with CM were characterized as "good" / "very good" and not active, respectively.


Assuntos
Cardiomiopatia Chagásica , Exercício Físico , Estilo de Vida
7.
Arq. bras. cardiol ; Arq. bras. cardiol;116(1): 68-74, Jan. 2021. tab, graf
Artigo em Inglês, Português | LILACS | ID: biblio-1152967

RESUMO

Resumo Fundamento Cardiomegalia pela radiografia de tórax (RXT) é preditor independente de morte em indivíduos com cardiomiopatia crônica da doença de Chagas (CCDC). Contudo, a correlação entre o aumento do índice cardiotorácico (ICT) na RXT e do diâmetro telediastólico do ventrículo esquerdo (DDVE) pela ecocardiografia (ECO) nessa população não está bem definida. Objetivos Analisar a relação entre cardiomegalia pela RXT e DDVE pela ECO em pacientes com doença de Chagas (DC) e sua aplicabilidade ao escore de Rassi. Métodos Estudo retrospectivo incluiu 63 pacientes ambulatoriais com DC avaliados por RXT e ECO. Cardiomegalia na RXT foi definida como ICT > 0,5. DDVE foi avaliado como variável contínua. Curva ROC foi utilizada para avaliar o potencial do DDVE para identificação de cardiomegalia pela RXT, com ponto de corte definido pela maior somatória de sensibilidade e especificidade. Resultados Idade mediana = 61 anos [intervalo interquartil: 48-68], 56% mulheres. CCDC foi identificada em 58 pacientes; 5 tinham a forma indeterminada da DC. Cardiomegalia foi detectada em 28 indivíduos. A área sob a curva ROC do DDVE para identificação de cardiomegalia foi de 0,806 (IC 95%: 0,692-0,919). O ponto de corte ótimo para DDVE foi de 60 mm (sensibilidade = 64%, especificidade = 89%). O uso do DDVE pela ECO em substituição ao ICT pela RXT alterou o escore de Rassi em 14 pacientes, e em 10 deles houve redução do risco presumido. Conclusão DDVE pela ECO é parâmetro adequado e com alta especificidade para distinguir entre presença e ausência de cardiomegalia na RXT na DC. (Arq Bras Cardiol. 2021; 116(1):68-74)


Abstract Background Cardiomegaly on chest X-ray is an independent predictor of death in individuals with chronic Chagas cardiomyopathy (CCC). However, the correlation between increased cardiothoracic ratio (CTR) on chest X-ray and left ventricular end-diastolic diameter (LVEDD) on echocardiography is not well established in this population. Objectives To assess the relationship between chest X-ray and LVEDD on echocardiography in patients with Chagas disease and its applicability to the Rassi score. Methods Retrospective study on 63 Chagas disease outpatients who underwent chest X-ray and echocardiography. Cardiomegaly on chest X-ray was defined as a CTR>0.5. LVEDD was analyzed as a continuous variable. ROC curve was used to evaluate the ability of LVEDD in detecting cardiomegaly by chest X-ray, with a cut-off point defined by the highest sum of sensitivity and specificity. Results Median age 61 years [interquartile range 48-68], 56% were women. CCC was detected in 58 patients, five patients had the indeterminate form of Chagas disease. Cardiomegaly was detected in 28 patients. The area under the ROC curve for LVEDD was 0.806 (95%CI: 0.692-0.919). The optimal cut-off for LVEDD was 60 mm (sensitivity = 64%, specificity = 89%). The use of LVEDD on echocardiography as a surrogate for CTR on chest X-ray changed the Rassi score values of 14 patients, with a reduction in the presumed risk in 10 of them. Conclusion LVEDD on echocardiography is an appropriate, highly specific parameter to distinguish between the presence and absence of cardiomegaly on chest X-ray in Chagas disease. (Arq Bras Cardiol. 2021; 116(1):68-74)


Assuntos
Humanos , Masculino , Feminino , Ecocardiografia , Doença de Chagas/diagnóstico por imagem , Raios X , Estudos Retrospectivos , Cardiomegalia/diagnóstico por imagem , Pessoa de Meia-Idade
8.
Infect Genet Evol ; 88: 104671, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33301989

RESUMO

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the chronic phase of disease, while most infected people do not present symptoms, characterizing the asymptomatic form, some patients develop the cardiac form or chronic chagasic cardiomyopathy, which is considered the most severe manifestation of this disease. Considering that the activation of the PI3Kγ signaling pathway is essential for an efficient immune response against T. cruzi infection, we evaluated the PIK3CG C > T (rs1129293) polymorphism in exon 3 of this gene, which encodes the catalytic subunit of PI3Kγ. The PIK3CG CT and TT genotypes were found to be associated with an increased risk of developing the cardiac form of the disease rather than the asymptomatic or digestive forms. In conclusion, the presence of the T allele at single or double doses may differentiate the cardiac from other clinical manifestations of Chagas disease. This finding should help in further studies to evaluate the mechanisms underlying the differential association of PIK3CG in Chagas disease.


Assuntos
Domínio Catalítico/genética , Cardiomiopatia Chagásica/genética , Doença de Chagas/genética , Doença de Chagas/parasitologia , Classe Ib de Fosfatidilinositol 3-Quinase/genética , Polimorfismo de Nucleotídeo Único , Trypanosoma cruzi , Cardiomiopatia Chagásica/parasitologia , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Variação Genética , Genótipo , Coração/parasitologia , Interações Hospedeiro-Parasita , Humanos , Doenças Negligenciadas/genética , Doenças Negligenciadas/parasitologia , Transdução de Sinais
9.
Front Immunol ; 11: 572178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072115

RESUMO

IL-10 is an anti-inflammatory cytokine that plays a significant role in the modulation of the immune response in many pathological conditions, including infectious diseases. Infection with Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, results in an ongoing inflammatory response that may cause heart dysfunction, ultimately leading to heart failure. Given its infectious and inflammatory nature, in this work we analyzed whether the lack of IL-10 hinders the anti-inflammatory effects of fenofibrate, a PPARα ligand, in a murine model of Chagas heart disease (CHD) using IL-10 knockout (IL-10 KO) mice. Our results show fenofibrate was able to restore the abnormal cardiac function displayed by T. cruzi-infected mice lacking IL-10. Treatment with fenofibrate reduced creatine kinase (CK) levels in sera of IL-10 KO mice infected with T. cruzi. Moreover, although fenofibrate could not modulate the inflammatory infiltrates developing in the heart, it was able to reduce the increased collagen deposition in infected IL-10 KO mice. Regarding pro-inflammatory mediators, the most significant finding was the increase in serum IL-17. These were reduced in IL-10 KO mice upon fenofibrate treatment. In agreement with this, the expression of RORγt was reduced. Infection of IL-10 KO mice increased the expression of YmI, FIZZ and Mannose Receptor (tissue healing markers) that remained unchanged upon treatment with fenofibrate. In conclusion, our work emphasizes the role of anti-inflammatory mechanisms to ameliorate heart function in CHD and shows, for the first time, that fenofibrate attains this through IL-10-dependent and -independent mechanisms.


Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Fenofibrato/uso terapêutico , Hipolipemiantes/uso terapêutico , Interleucina-10/metabolismo , Miocárdio/patologia , Trypanosoma cruzi/fisiologia , Tripanossomíase/tratamento farmacológico , Animais , Células Cultivadas , Cardiomiopatia Chagásica/imunologia , Creatina Quinase/sangue , Modelos Animais de Doenças , Humanos , Interleucina-10/genética , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Tripanossomíase/imunologia , Cicatrização
10.
Trop Med Infect Dis ; 5(3)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824760

RESUMO

Background-Patients with Chagas cardiomyopathy (CC) have high mortality, and CC is a common indication for heart transplantation (HTx) in endemic countries. Chagas disease reactivation (CDR) is common after transplantation and is likely to cause adverse outcomes unless detected and treated appropriately. This study reviews our experiences with HTx among patients with CC, and the use of benznidazole (BZ) before transplantation. Methods-During the 18-year period from 1996 through 2014, 70 of 353 patients who underwent HTx (19.8%) had CC, and 53 patients met the inclusion criteria. The effectiveness of prophylactic treatment with BZ (dose of 5 mg/kg/day, two times per day, for at least four weeks and for a maximum of eight weeks) was determined based on the observed reduction in the incidence of CDR during the post-HTx period. Results-Prophylactic therapy was administered to 18/53 patients (34.0%). During the follow-up period, the incidence rate of CDR in our study was 34.0% (18/53). Based on logistic regression analysis, only prophylaxis (OR = 0.12; CI 0.02-0.76; p = 0.025) was considered to protect against CDR. Conclusion-Our study suggests that the use of BZ may reduce the incidence of CDR in patients undergoing HTx and warrants further investigation in a prospective, randomized trial.

11.
Cells ; 9(7)2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32645832

RESUMO

Chagas disease discovered more than a century ago remains an incurable disease. The objective of this work was to investigate the therapeutic potential of cardiomyocytes derived from mouse embryonic stem cells (CM-mESC) in a model of chronic Chagasic cardiomyopathy (CCC). Mouse embryonic stem cells (mESC) were characterized, transduced with luciferase, and submitted to cardiac differentiation. CM-mESC were labeled with superparamagnetic iron oxide particles. To induce CCC, mice were infected with Brazil strain trypomastigotes. At 150 days post-infection (dpi), infected animals were treated with CM-mESC or PBS. Cells were detected by magnetic resonance imaging (MRI) and bioluminescence. Cardiac function was evaluated by MRI and electrocardiogram at 150 and 196 dpi. CCC mice showed significant differences in MRI and ECG parameters compared to non-infected mice. However, no differences were observed in contractile and electrical parameters between cell and PBS injected groups, 45 days after cell transplantation. Cells were detected 24 h after transplantation by MRI. CM-mESC bioluminescence tracking demonstrated over 90% decrease in signal 8 days after treatment. Nevertheless, the Infected + CM-mESC group showed a significant reduction in the percentage of collagen fibers when compared to the Infected + PBS group. In conclusion, CM-mESC therapy was not effective in reversing cardiac functional changes induced by Chagas disease despite some improvement in myocardial fibrosis.


Assuntos
Cardiomiopatias/metabolismo , Cardiomiopatias/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Miócitos Cardíacos/fisiologia , Animais , Cardiomiopatias/diagnóstico por imagem , Doença de Chagas/diagnóstico por imagem , Doença de Chagas/metabolismo , Doença de Chagas/terapia , Modelos Animais de Doenças , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Feminino , Citometria de Fluxo , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Miócitos Cardíacos/metabolismo
12.
Trop Med Infect Dis ; 5(3)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610473

RESUMO

Chagas disease, caused by a Trypanosona cruzi infection, is one of the main causes of heart failure in Latin America. It was originally a health problem endemic to South America, predominantly affecting residents of poor rural areas. With globalization and increasing migratory flows from these areas to large cities, the immigration of T. cruzi chronically-infected people to developed, non-endemic countries has occurred. This issue has emerged as an important consideration for heart transplant professionals. Currently, Chagas patients with end-stage heart failure may need a heart transplantation (HTx). This implies that in post-transplant immunosuppression therapy to avoid rejection in the recipient, there is the possibility of T. cruzi infection reactivation, increasing the morbidity and mortality rates. The management of heart transplant recipients due to Chagas disease requires awareness for early recognition and parasitic treatment of T. cruzi infection reactivation. This issue poses challenges for heart transplant professionals, especially regarding the differential diagnosis between rejection and reactivation episodes. The aim of this review is to discuss the complexity of the Chagas disease reactivation phenomenon in patients submitted to HTx for end-stage chagasic cardiomyopathy.

13.
Rev. costarric. cardiol ; 22(1)jun. 2020.
Artigo em Espanhol | LILACS, SaludCR | ID: biblio-1388997

RESUMO

Resumen La enfermedad de Chagas es un problema de salud pública en Latinoamérica, donde afecta a aproximadamente a 6 millones de personas. En Costa Rica se ha descrito la enfermedad desde 1941, con varios reportes de casos confirmados agudos y crónicos. La miocardiopatía chagásica afecta al 30% de los individuos con infección crónica y es la manifestación más grave de la enfermedad, con una morbimortalidad mayor que otras miocardiopatías. La resonancia magnética cardíaca, debido a su capacidad de caracterización tisular permite identificar con alta correlación histopatológica la presencia de fibrosis, edema e inflamación en la miocardiopatía chagásica. Esto ha permitido una mejor comprensión de la compleja fisiopatología de la enfermedad y además permite el diagnóstico diferencial con otras patologías simuladoras como lo es la cardiopatía isquémica. En la MCh la presencia de fibrosis miocárdica predice de manera independiente eventos adversos mayores tales como taquicardia ventricular sostenida y muerte cardiovascular. Debido a lo anterior la resonancia magnética cardíaca es una robusta herramienta capaz de mejorar el diagnóstico, la estratificación de riesgo y el pronóstico de estos pacientes, con miras a mejores y oportunas intervenciones terapéuticas.


Abstract Chagas disease is a public health problem in Latin America, where it affects approximately 6 million people. In Costa Rica the disease has been described since 1941, with several reports of acute and chronic confirmed cases. Chagas cardiomyopathy affects 30% of individuals with chronic infection and is the most serious manifestation of the disease, with a higher morbidity and mortality than other cardiomyopathies. Cardiac magnetic resonance, due to its capacity for tissue characterization, identifies the presence of fibrosis, aedema and inflammation in Chagas cardiomyopathy with high histopathological correlation. This has allowed a better understanding of the complex pathophysiology of the disease and also allows differential diagnosis with other pathologies that can simulate, such as ischemic heart disease. In Chagas cardiomyopathy, the presence of myocardial fibrosis independently predicts major adverse events such as sustained ventricular tachycardia and cardiovascular death. Due to the above, cardiac magnetic resonance is a robust tool capable of improving the diagnosis, risk stratification and prognosis of these patients, with a view to better and timely therapeutic interventions.


Assuntos
Humanos , Espectroscopia de Ressonância Magnética/uso terapêutico , Cardiomiopatia Chagásica/diagnóstico por imagem , Doença de Chagas/terapia
14.
Eur Heart J Case Rep ; 4(1): 1-5, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32467867

RESUMO

BACKGROUND: Patients with end-stage heart failure, suffering from severe pulmonary hypertension (PH) and elevated pulmonary vascular resistance, are not eligible for heart transplant due to high mortality risk and primary graft dysfunction. Severe PH may be favoured by functional severe mitral regurgitation, which is present in many cardiopathies like end-stage Chagasic cardiomyopathy. CASE SUMMARY: We present a case of a young man with end-stage heart failure secondary to Chagas cardiomyopathy with severe functional mitral regurgitation (FMR) and severe PH. The patient received percutaneous correction with MitraClip® system reducing PH and making him a suitable candidate for heart transplant. DISCUSSION: In patients with advanced heart failure, FMR, and severe PH, optimal treatment according to current guide lines is recommended. MitraClip® therapy appears to be safe and effective for control of severe PH as a bridge measure for cardiac transplantation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31616643

RESUMO

Background: The failure to translate preclinical results to the clinical setting is the rule, not the exception. One reason that is frequently overlooked is whether the animal model reproduces distinctive features of human disease. Another is the reproducibility of the method used to measure treatment effects in preclinical studies. Left ventricular (LV) function improvement is the most common endpoint in preclinical cardiovascular disease studies, while echocardiography is the most frequently used method to evaluate LV function. In this work, we conducted a robust echocardiographic evaluation of LV size and function in dogs chronically infected by Trypanosoma cruzi. Methods and Results: Echocardiography was performed blindly by two distinct observers in mongrel dogs before and between 6 and 9 months post infection. Parameters analyzed included end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), and fractional shortening (FS). We observed a significant LVEF and FS reduction in infected animals compared to controls, with no significant variation in volumes. However, the effect of chronic infection in systolic function was quite variable, with EF ranging from 17 to 66%. Using the cut-off value of EF ≤ 40%, established for dilated cardiomyopathy (DCM) in dogs, only 28% of the infected dogs were affected by the chronic infection. Conclusions: The canine model of CCC mimics human disease, reproducing the percentage of individuals that develop heart failure during the chronic infection. It is thus mandatory to establish inclusion criteria in the experimental design of canine preclinical studies to account for the variable effect that chronic infection has on systolic function.


Assuntos
Cardiomiopatia Chagásica/diagnóstico por imagem , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Cães , Reprodutibilidade dos Testes , Função Ventricular
16.
Life Sci ; 232: 116629, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276687

RESUMO

AIMS: To investigate the effects of moderate aerobic physical training on cardiac function and morphology as well as on the levels of glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) of animals infected with the Y strain of Trypanosoma cruzi. MAIN METHODS: Twenty-eight male C57BL/6 mice were distributed into 4 groups: sedentary control (SC), trained control (TC), sedentary infected (CHC) and trained infected (CHT). The infection was performed by intraperitoneal injection of trypomastigote forms and the animals were adapted to treadmill in the week before the beginning of the training protocol, initiated 45 days post infection. Maximal exercise test (TEM) was performed at the baseline as well as at the end of the 4th, 8th and 12th weeks of training. At the end of the 12th week, all animals were evaluated for cardiac morphology and function by echocardiography. KEY FINDINGS: CHC group showed a larger area of right ventricle (RVA), increased end-systolic volume and reduction in ejection fraction (EF), stroke volume (SV), cardiac output (CO) and fractional area change (FAC). The training reduced the RVA and improved the FAC of chagasic animals. GDNF level was higher in TC and CHC groups compared to SC in heart and BDNF levels were higher in CHC compared to SC in heart and serum. SIGNIFICANCE: Physical training ameliorated the cardiac function of infected animals and promoted adjusts in BDNF and GDNF levels. These findings evidenced these neurotrophins as possible biomarkers of cardiac function responsive to exercise stimulus.


Assuntos
Tolerância ao Exercício/fisiologia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Animais , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Débito Cardíaco , Doença de Chagas/metabolismo , Modelos Animais de Doenças , Ecocardiografia , Teste de Esforço , Fator Neurotrófico Derivado de Linhagem de Célula Glial/análise , Fator Neurotrófico Derivado de Linhagem de Célula Glial/fisiologia , Coração/fisiologia , Testes de Função Cardíaca , Ventrículos do Coração/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Neural/análise , Fator de Crescimento Neural/fisiologia , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/fisiologia , Volume Sistólico/fisiologia , Trypanosoma cruzi/patogenicidade
17.
Front Immunol ; 10: 800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057540

RESUMO

Background: Chagas cardiomyopathy is the main fibrosing myocarditis among known heart diseases. Development of cardiomyopathy has been related to extracellular matrix (ECM) remodeling, which are controlled by matrix metalloproteinases (MMPs) and cytokines, especially interleukin (IL)-1ß. The convertion of 31KDa inactive precursor, the proIL-1ß in 17KDa active IL-1ß peptide, is controlled by caspase-1-dependent pathway, associated with inflammasomes. Other caspase-1 independent mechanisms mediated by proteases, especially as MMPs, have already been described. Methods: We evaluated IL-1ß activation pathways in neutrophils and monocyte subsets from patients with different clinical forms of Chagas disease after T. cruzi antigen stimulation by multiparameter flow cytometry. Results: Our data demonstrated that Chagas patients with the indeterminate clinical form (IND) showed increased levels of IL-1ß post-stimulation as well as increased expression of MMP-2, NLRP3, and CASP1, which are associated with the classical caspase-1-dependent pathway. Conversely, patients with the cardiac clinical form (CARD) showed increased IL-1ß after stimulation associated with MMP-9 and alternative caspase-1-independent pathway. Conclusions: We suggest some distinct molecular mechanisms for production of IL-1ß in innate immune cells from patients with different clinical forms of Chagas disease. MMP-2 and MMP-9 gelatinases are associated with distinct disease outcomes and IL-1ß production.


Assuntos
Cardiomiopatia Chagásica/imunologia , Doença de Chagas/imunologia , Imunidade Inata/imunologia , Interleucina-1beta/imunologia , Adulto , Idoso , Caspase 1/imunologia , Citocinas/imunologia , Feminino , Humanos , Inflamassomos/imunologia , Masculino , Metaloproteinase 2 da Matriz/imunologia , Metaloproteinase 9 da Matriz/imunologia , Pessoa de Meia-Idade , Monócitos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Neutrófilos/imunologia , Trypanosoma cruzi/imunologia
18.
Insuf. card ; 14(1): 12-33, mar. 2019. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1012280

RESUMO

Acorde al último reporte epidemiológico de la Organización Mundial de la Salud del año 2015, en Argentina existen 1,5 millones de personas infectadas por el Trypanosoma cruzi y alrededor de 370.000 pacientes con distintas manifestaciones de la enfermedad de Chagas. El objetivo de esta revisión es analizar una de las manifestaciones clínicas más graves e invalidantes de esta enfermedad: la miocardiopatía chagásica crónica. Esta patología, que presenta una distribución geográfica dispar en la Argentina, comparte varias características comunes con otras formas etiológicas de insuficiencia cardíaca, aunque su epidemiología, presentación clínica y respuesta al tratamiento médico, eléctrico y quirúrgico le otorgan una distinción particular y en muchos casos, poco conocida. Por tal motivo, existe en la comunidad médica, un creciente interés en alcanzar un mayor conocimiento de esta enfermedad a fin de implementar manejos y decisiones terapéuticas, que si bien demostraron beneficio en otras poblaciones de pacientes con insuficiencia cardíaca, aun no han sido adecuadamente avaladas para su aplicación en insuficiencia cardíaca chagásica. Muchas de las indicaciones e intervenciones se basan en experiencia más que evidencia científica. Es por ello que esta revisión es un desafío oportuno para optimizar el tratamiento y pronóstico de esta población.


According to the last epidemiological report of the World Health Organization in 2015, in Argentina there are 1.5 million people infected with Trypanosoma cruzi and around 370,000 patients with different manifestations of Chagas disease. The objective of this review is to analyze one of the most serious and invalidating clinical manifestations of this disease: chronic chagasic myocardiopathy. This pathology, which has a disparate geographical distribution in Argentina, shares several common characteristics with other etiological forms of heart failure, although its epidemiology, clinical presentation and response to medical, electrical and surgical treatment give it a particular distinction and in many cases, little known. For this reason, there is a growing interest in the medical community to achieve greater knowledge of this disease in order to implement management and therapeutic decisions, which although they have shown benefit in other populations of patients with heart failure, have not yet been adequately endorsed. for its application in chagasic heart failure. Many of the indications and interventions are based on experience rather than scientific evidence. That is why this review is a timely challenge to optimize the treatment and prognosis of this population.


De acordo o último relatório epidemiológico da Organização Mundial da Saúde em 2015, na Argentina existem 1,5 milhão de pessoas infectadas pelo Trypanosoma cruzi e cerca de 370.000 pacientes com manifestações diferentes da doença de Chagas. O objetivo desta revisão é analisar uma das manifestações clínicas mais graves e invalidantes dessa doença: miocardiopatia chagásica crônica. Esta condição, que tem uma distribuição geográfica desigual na Argentina, compartilha várias características comuns com outras formas etiológicos de insuficiência cardíaca, embora sua epidemiologia, apresentação clínica e resposta ao tratamento médico, elétrico e cirúrgico dar uma distinção especial e, em muitos casos, pouco conhecido. Portanto, há na comunidade médica, um crescente interesse na obtenção de uma melhor compreensão da doença, a fim de implementar as decisões de manejo e tratamento, que embora benefício mostrou em outras populações de pacientes com insuficiência cardíaca ainda não foram adequadamente apoiados para sua aplicação na insuficiência cardíaca chagásica. Muitas das indicações e intervenções são baseadas na experiência e não na evidência científica. É por isso que esta revisão é um desafio oportuno para otimizar o tratamento e o prognóstico dessa população.

19.
Parasitology ; 146(3): 269-283, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30210012

RESUMO

Chagas disease is a complex tropical pathology caused by the kinetoplastid Trypanosoma cruzi. This parasite displays massive genetic diversity and has been classified by international consensus in at least six Discrete Typing Units (DTUs) that are broadly distributed in the American continent. The main clinical manifestation of the disease is the chronic chagasic cardiomyopathy (CCC) that is lethal in the infected individuals. However, one intriguing feature is that only 30-40% of the infected individuals will develop CCC. Some authors have suggested that the immune response, host genetic factors, virulence factors and even the massive genetic heterogeneity of T. cruzi are responsible of this clinical pattern. To date, no conclusive data support the reason why a few percentages of the infected individuals will develop CCC. Therefore, we decided to conduct a systematic review analysing the host genetic factors, immune response, cytokine production, virulence factors and the plausible association of the parasite DTUs and CCC. The epidemiological and clinical implications are herein discussed.


Assuntos
Cardiomiopatias/parasitologia , Doença de Chagas/imunologia , Citocinas/imunologia , Heterogeneidade Genética , Imunidade Inata , Trypanosoma cruzi/genética , Fatores de Virulência/imunologia , Cardiomiopatias/imunologia , Doença de Chagas/parasitologia , Interações Hospedeiro-Parasita , Humanos
20.
ESC Heart Fail ; 5(3): 249-256, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29266804

RESUMO

AIMS: The SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients. METHODS AND RESULTS: SHIFT was a randomized, double-blind, placebo-controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta-blocker. ChD HF presented a poor prognosis (all-cause mortality at 2 years was ~60%). The mean twice-daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all-cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope. CONCLUSIONS: ChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit-risk profile in ChD HF patients.


Assuntos
Doença de Chagas/complicações , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Ivabradina/administração & dosagem , Volume Sistólico/efeitos dos fármacos , Argentina/epidemiologia , Brasil/epidemiologia , Fármacos Cardiovasculares/administração & dosagem , Doença de Chagas/diagnóstico , Doença de Chagas/fisiopatologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/etiologia , Insuficiência Cardíaca Sistólica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Resultado do Tratamento , Função Ventricular Esquerda
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