Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease.

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health problem for which there is no effective treatment in the chronic stage. Intense cardiac fibrosis and inflammation are hallmarks of chronic Chagas disease cardiomyopathy (CCC). Previously, we identified upregulation of circulating and cardiac miR-21, a pro-fibrotic microRNA (miRNA), in subjects with CCC. Here, we explored the potential role of miR-21 as a therapeutic target in a model of chronic Chagas disease. PCR array-based 88 microRNA screening was performed in heart samples obtained from C57Bl/6 mice chronically infected with T. cruzi and serum samples collected from CCC patients. MiR-21 was found upregulated in both human and mouse samples, which was corroborated by an in silico analysis of miRNA-mRNA target prediction. In vitro miR-21 functional assays (gain-and loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and collagen expression upon transforming growth factor beta 1 (TGFß1) and T. cruzi stimulation, while miR-21 blockage reduced collagen expression. Finally, treatment of T. cruzi-infected mice with locked nucleic acid (LNA)-anti-miR-21 inhibitor promoted a significant reduction in cardiac fibrosis. Our data suggest that miR-21 is a mediator involved in the pathogenesis of cardiac fibrosis and indicates the pharmacological silencing of miR-21 as a potential therapeutic approach for CCC.

Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy.

Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.

Image-guided percutaneous intralesional administration of mesenchymal stromal cells in subjects with chronic complete spinal cord injury: a pilot study.

BACKGROUND AIMS: The potential of cell therapies to improve neurological function in subjects with spinal cord injury (SCI) is currently under investigation. In this context, the choice of cell type, dose, route and administration regimen are key factors. Mesenchymal stromal cells (MSCs) can be easily obtained, expanded and are suitable for autologous transplantation. Here we conducted a pilot study that evaluated safety, feasibility and potential efficacy of intralesional MSCs transplantation performed through image-guided percutaneous injection, in subjects with chronic complete SCI. METHODS: Five subjects with chronic traumatic SCI (>6 months), at thoracic level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A, complete injury, were included. Somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Autologous MSCs were injected directly into the lesion site through percutaneous injection guided by computerized tomography (CT). RESULTS: Tomography-guided percutaneous cell transplantation was a safe procedure without adverse effects. All subjects displayed improvements in spinal cord independence measure (SCIM) scores and functional independence measure (FIM), mainly due to improvements in bowel movements and regularity. Three subjects showed improved sensitivity to tactile stimulation. Two subjects improved AIS grade to B, incomplete injury, although this was sustained in only one of them during the study follow-up. CONCLUSION: Autologous bone marrow MSC transplantation, performed through CT-guided percutaneous injection, was shown to be safe and feasible. Further studies are required to demonstrate efficacy of this therapeutic scheme.

Evaluation of Galectin-3 as a Novel Biomarker for Chagas Cardiomyopathy.

OBJECTIVES: Chagas cardiomyopathy has worse long-term outcomes than other cardiomyopathies. A biomarker strategy to refer subjects for noninvasive cardiac imaging may help in the early identification of cardiac damage in subjects with Chagas disease. Galectin-3 (Gal-3) is a mediator of cardiac fibrosis shown to be upregulated in animal models of decompensated heart failure. Here we assessed the correlation of Gal-3 with myocardial fibrosis in patients with Chagas disease. METHODS: This study comprised 61 subjects with Chagas disease. All subjects underwent clinical assessments, Doppler echocardiography and magnetic resonance imaging. Plasmatic Gal-3 was determined by ELISA. RESULTS: Delayed enhancement (DE) was identified in 37 of 61 subjects (64%). The total amount of myocardial fibrosis was 9.4% [interquartile interval (IQI): 2.4-18.4]. No differences were observed in Gal-3 concentration according to the presence or absence of myocardial fibrosis, with a median Gal-3 concentration of 11.7 ng/ml (IQI: 9.4-15) in subjects with DE versus 12.9 ng/ml (IQI: 9.2-14) in subjects without DE (p = 0.18). No correlation was found between myocardial fibrosis and Gal-3 concentration (r = 0.098; p = 0.47). CONCLUSIONS: There is no correlation between the degree of myocardial fibrosis and the concentration of Gal-3 in subjects with Chagas disease.

Transplantation of autologous mesenchymal stromal cells in complete cervical spinal cord injury: a pilot study.

Objective: Spinal cord injury (SCI) is a serious condition that can lead to partial or complete paraplegia or tetraplegia. Currently, there are few therapeutic options for these conditions, which are mainly directed toward the acute phase, such as surgical intervention and high-dose steroid administration. Mesenchymal stromal cells (MSC) have been shown to improve neurological function following spinal cord injury. The aim of the study was to evaluate the safety, feasibility, and potential efficacy of MSC transplantation in patients with cervical traumatic SCI. Methods: We included seven subjects with chronic traumatic SCI (> 1 year) at the cervical level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A. Subjects received two doses of autologous bone marrow derived MSC, the first by direct injection into the lesion site after hemilaminectomy and the second three months later by intrathecal injection. Neurologic evaluation, spinal magnetic resonance imaging (MRI), urodynamics, and life quality questionnaires were assessed before and after treatment. Results: Cell transplantation was safe without severe or moderate adverse effects, and the procedures were well tolerated. Neurological evaluation revealed discrete improvements in sensitivity below the lesion level, following treatment. Five subjects showed some degree of bilateral sensory improvement for both superficial and deep mechanical stimuli compared to the pretreatment profile. No significant alterations in bladder function were observed during this study. Conclusion: Transplantation of autologous MSC in patients with chronic cervical SCI is a safe and feasible procedure. Further studies are required to confirm the efficacy of this therapeutic approach. Clinical trial registration: https://clinicaltrials.gov/study/NCT02574572, identifier NCT02574572.

Clinical Trials Using Mesenchymal Stem Cells for Spinal Cord Injury: Challenges in Generating Evidence.

Spinal cord injury (SCI) remains an important public health problem which often causes permanent loss of muscle strength, sensation, and function below the site of the injury, generating physical, psychological, and social impacts throughout the lives of the affected individuals, since there are no effective treatments available. The use of stem cells has been investigated as a therapeutic approach for the treatment of SCI. Although a significant number of studies have been conducted in pre-clinical and clinical settings, so far there is no established cell therapy for the treatment of SCI. One aspect that makes it difficult to evaluate the efficacy is the heterogeneity of experimental designs in the clinical trials that have been published. Cell transplantation methods vary widely among the trials, and there are still no standardized protocols or recommendations for the therapeutic use of stem cells in SCI. Among the different cell types, mesenchymal stem/stromal cells (MSCs) are the most frequently tested in clinical trials for SCI treatment. This study reviews the clinical applications of MSCs for SCI, focusing on the critical analysis of 17 clinical trials published thus far, with emphasis on their design and quality. Moreover, it highlights the need for more evidence-based studies designed as randomized controlled trials and potential challenges to be addressed in context of stem cell therapies for SCI.

The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas' Disease: A Study Using Magnetic Resonance.

BACKGROUND: Previous data has shown that patients in the indeterminate form of Chagas disease may present myocardial fibrosis as shown on through magnetic resonance imaging (MRI). However, there is little information available regarding the degree of severity of myocardial fibrosis in these individuals. This variable has the potential to predict the evolution of Chagas' disease into its cardiac form. OBJECTIVES: To describe the frequency and extent of myocardial fibrosis evaluated using an MRI in patients in the indeterminate form, and to compare it with other forms of the disease. METHODS: Patients were admitted one after another. Their clinical history was collected and they were submitted to laboratory exams and an MRI. RESULTS: Sixty-one patients with Chagas' disease, with an average age of 58 ± 9 years old, 17 patients in the indeterminate form, 16 in the cardiac form without left ventricular (LV) dysfunction and 28 in the cardiac form with LV dysfunction were studied. P <0.05 was considered to be statistically significant. Late enhancement was detected in 37 patients (64%). Myocardial fibrosis was identified in 6 individuals in indeterminate form (41%; 95% CI 23-66) in a proportion similar to that observed in cardiac form without LV dysfunction (44%); p = 1.0. Among the individuals with fibrosis, the total area of the affected myocardium was 4.1% (IIQ: 2.1 - 10.7) in the indeterminate form versus 2.3% (IIQ: 1-5) in the cardiac form without LV (p = 0.18). The left ventricular fraction ejection in subjects in the indeterminate form was similar to that of the individuals in the cardiac form without ventricular dysfunction (p = 0.09). CONCLUSION: The presence of fibrosis in the indeterminate form of Chagas' disease has a frequency and extension similar to that of in the cardiac form without dysfunction, suggesting that the former is part of a subclinical disease spectrum, rather than lacking cardiac involvement.

SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease - 2023 / Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas ­ 2023

Em 2021, por iniciativa de seu então presidente, Dr. Marcelo Queiroga Cartaxo Lopes, a Sociedade Brasileira de Cardiologia (SBC) nos comissionou para a coordenação dos trabalhos, visando à elaboração da nova diretriz relativa à doença de Chagas (DC). Justificava-se a empreitada, uma vez que, desde 2011, a SBC não se responsabilizava diretamente por uma diretriz no contexto. Diversamente daquela, publicada há mais de uma década nos Arquivos Brasileiros de Cardiologia, a atual não mais seria "latino-americana", mas passaria a contar essencialmente "apenas" com contingente expressivo de colaboradores nacionais. A plêiade ilustre de investigadores ativos no contexto, que então convocamos, seria representativa de uma equipe ainda mais dilatada de profissionais dos mais diversificados pontos do país, que se envolvem e contribuem diretamente para o avanço no combate à DC, e passou a responder integralmente pela autoria desta diretriz, conforme explicitado abaixo.

Disjunção do anel mitral: modalidades diagnósticas, implicações clínicas e evolução prognóstica / Mitral annulus disjunction: diagnostic modalities, clinical implications, and prognostic progression

A disjunção do anel mitral (DAM) é uma inserção anormal da linha de flexão do anel mitral na parede atrial. O anel mostra uma separação (disjunção) entre a junção folheto posterior-parede atrial e a crista miocárdica ventricular esquerda.1 A DAM foi descrita pela primeira vez há mais de 30 anos em estudo de autópsia, estando relacionada com prolapso da valva mitral (PVM) em 92% dos casos.2 Desde então, foram realizados diversos estudos, sendo a prevalência de DAM em pacientes com PVM reportada de forma variável, podendo ou não estar associada à insuficiência mitral. O ecocardiograma transtorácico (ETT) faz parte da avaliação inicial do prolapso valvar mitral, permitindo o diagnóstico e a avaliação de complicações relacionadas. Com a evolução de novos métodos diagnósticos, a ressonância magnética cardíaca (RMC) e o ecocardiograma transesofágico (ETE) passaram a aprimorar a avaliação dessa patologia, bem como de sua extensão e localização. Contudo, as características fenotípicas do PVM que estão mais associadas a DAM permanecem incertas, sobretudo devido ao número limitado de pacientes, nos estudos clássicos sobre o tema. Portadores de DAM podem desenvolver sintomas relacionados a arritmias ventriculares, configurando a síndrome arrítmica da DAM (SDAM), podendo evoluir para morte súbita. Na literatura, os dados prognósticos ainda são conflitantes entre os diversos estudos acerca do tema, indo desde critérios claros de diagnóstico, o melhor método de imagem a ser aplicado, o tratamento e o prognóstico. Esta revisão descreve as características da DAM associada ou não ao prolapso valvar, auxiliando no diagnóstico e na conduta dessa importante patologia. (AU)

Mitral annulus disjunction (MAD) is an abnormal insertion of the flexion line of the mitral annulus into the atrial wall. The annulus presents a separation (disjunction) between the posterior leaflet­atrial wall junction and the left ventricular myocardial crest.1 MAD was first described more than 30 years ago in an autopsy study and is reportedly related to mitral valve prolapse (MVP) in 92% of cases.2 Since then, several studies have been conducted, and reports on the prevalence of MAD in patients with MVP have varied. Ultimately, it may or may not be associated with mitral regurgitation. Transthoracic echocardiography is part of initial MVP assessment, allowing its diagnosis and the assessment of related complications. As new diagnostic methods emerged, cardiac magnetic resonance imaging and transesophageal echocardiography improved the assessment of this pathology in terms of its diagnosis, extension, and location. However, the phenotypic characteristics of MVP that are more closely associated with MAD remain uncertain mainly due to the limited number of patients in classic studies on the subject. Patients with MAD may develop symptoms related to ventricular arrhythmias, configuring the MAD arrhythmic syndrome, which may progress to sudden death. The literature presents conflicting prognostic data among several studies on the subject from clear diagnostic criteria and best imaging method to be used to treatment and prognosis. This review describes MAD characteristics associated (or not) with valve prolapse to improve the diagnosis and management of this important pathology. (AU)

Lack of association between serum syndecan-4, myocardial fibrosis and ventricular dysfunction in subjects with chronic Chagas disease.

BACKGROUND: Syndecan-4 is a transmembrane glycoprotein associated with inflammation and fibrosis. Increased syndecan-4 levels were previously detected after acute myocardial infarction and in subjects with heart failure. However, the levels of syndecan-4 in subjects with Chagas disease have not so far been investigated. The aim of this study was to investigate the potential role of serum sydencan-4 as a novel biomarker for myocardial fibrosis and cardiac dysfunction in subjects with Chagas disease. METHODS: This study comprised subjects with Chagas disease (n = 56), being 14 (25%) with the indeterminate form, 16 (29%) with the cardiac form without ventricular dysfunction, and 26 (46%) with the cardiac form with ventricular dysfunction. RESULTS: Syndecan-4 serum concentrations did not correlate with presence or absence of myocardial fibrosis (P = 0.386) nor disease severity in subjects with Chagas disease (P = 0.918). Additionally, no correlation was found either between the degree of myocardial fibrosis and serum syndecan-4 [r = 0.08; P = 0.567] or between left ventricular ejection fraction and syndecan-4 [r = 0.02; P = 0.864]. In contrast, NT-proBNP levels correlated with ejection fraction and myocardial fibrosis. CONCLUSIONS: Our results demonstrate the lack of correlations between serum syndecan-4, myocardial fibrosis and cardiac dysfunction in subjects with Chagas disease. Further studies are required to show if syndecan-4 concentrations can be marker for prognosis assessment or disease progression.

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease.

BACKGROUND: Galectin-3, a ß-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated. OBJECTIVE: The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease. METHODS: Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene. RESULTS: For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease. CONCLUSION: Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease.

The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas' Disease: A Study Using Magnetic Resonance / Presença e Extensão da Fibrose Miocárdica na Forma Indeterminada da Doença de Chagas: Estudo de Ressonância Magnética

Abstract Background: Previous data has shown that patients in the indeterminate form of Chagas disease may present myocardial fibrosis as shown on through magnetic resonance imaging (MRI). However, there is little information available regarding the degree of severity of myocardial fibrosis in these individuals. This variable has the potential to predict the evolution of Chagas' disease into its cardiac form. Objectives: To describe the frequency and extent of myocardial fibrosis evaluated using an MRI in patients in the indeterminate form, and to compare it with other forms of the disease. Methods: Patients were admitted one after another. Their clinical history was collected and they were submitted to laboratory exams and an MRI. Results: Sixty-one patients with Chagas' disease, with an average age of 58 ± 9 years old, 17 patients in the indeterminate form, 16 in the cardiac form without left ventricular (LV) dysfunction and 28 in the cardiac form with LV dysfunction were studied. P <0.05 was considered to be statistically significant. Late enhancement was detected in 37 patients (64%). Myocardial fibrosis was identified in 6 individuals in indeterminate form (41%; 95% CI 23-66) in a proportion similar to that observed in cardiac form without LV dysfunction (44%); p = 1.0. Among the individuals with fibrosis, the total area of the affected myocardium was 4.1% (IIQ: 2.1 - 10.7) in the indeterminate form versus 2.3% (IIQ: 1-5) in the cardiac form without LV (p = 0.18). The left ventricular fraction ejection in subjects in the indeterminate form was similar to that of the individuals in the cardiac form without ventricular dysfunction (p = 0.09). Conclusion: The presence of fibrosis in the indeterminate form of Chagas' disease has a frequency and extension similar to that of in the cardiac form without dysfunction, suggesting that the former is part of a subclinical disease spectrum, rather than lacking cardiac involvement.

Resumo Fundamento: Dados prévios têm demonstrado que pacientes na forma indeterminada podem apresentar fibrose miocárdica à ressonância magnética (RM). No entanto, são poucas as informações disponíveis quanto ao grau de fibrose miocárdica apresentada por esses indivíduos, o que guardaria relação com o potencial dessa variável na predição de evolução para a forma cardíaca da doença de Chagas. Objetivos: Descrever a frequência e extensão da fibrose miocárdica avaliada por RM em pacientes da forma indeterminada, comparando com as outras formas da doença. Métodos: Pacientes consecutivamente admitidos tiveram história clínica colhida e foram submetidos à realização de exames laboratoriais e RM. Resultados: Foram estudados 61 pacientes portadores da doença de Chagas, com média de idade de 58 ± 9 anos, sendo 17 pacientes na forma indeterminada, 16 na forma cardíaca sem disfunção do ventrículo esquerdo (VE) e 28 na forma com disfunção do VE. Foi considerado estatisticamente significante p < 0,05. Realce tardio foi detectado em 37 pacientes (64%). Foi identificada fibrose miocárdica em 6 indivíduos na forma indeterminada (41%; IC95% 23 - 66), proporção semelhante à observada na forma cardíaca sem disfunção do VE (44%); p = 1,0. Entre os indivíduos com fibrose, a área total do miocárdio acometida foi de 4,1% (IIQ: 2,1 - 10,7) na forma indeterminada versus 2,3% (IIQ: 1 - 5) na forma cardíaca sem disfunção do VE (p = 0,18). A fração de ejeção do ventrículo esquerdo nos indivíduos na forma indeterminada foi semelhante aos portadores da forma cardíaca sem disfunção ventricular (p = 0,09). Conclusão: A presença de fibrose na forma indeterminada da doença de Chagas tem frequência e extensão semelhante à forma cardíaca sem disfunção, o que sugere que a primeira faz parte de um espectro de doença subclínica, em vez da ausência de acometimento cardíaco.

Avaliação da eficácia da terapia com g-csf para a melhora dos sintomas em pacientes portadores de cardiomiopatia chagásica crônica: ensaio clínico fase ii, prospectivo, bicêntrico, duplo-cego, randomizado e controlado por placebo

INTRODUÇÃO: A cardiomiopatia chagásica crônica (CCC) é uma condição clínica potencialmente fatal, sendo responsável pela maior parte da morbimortalidade da doença de Chagas crônica.. Apesar do mecanismo fisiopatogênico único, o tratamento padrão da CCC é semelhante ao esquema terapêutico para insuficiência cardíaca (IC) de outras etiologias. Sendo uma doença negligenciada, uma nova abordagem terapêutica é de extrema necessidade, e o reposicionamento de medicamentos já usados na prática clínica é uma estratégia de pesquisa muito usada atualmente por ser considerada mais rápida e potencialmente eficaz para o desenvolvimento de um novo tratamento. Estudos anteriores mostraram que o fator estimulador de colônias de granulócitos (G-CSF) melhora a função cardíaca em modelos animais de CCC e também em ensaios clínicos de IC de outras etiologias. Nesse estudo, realizamos um ensaio randomizado duplo-cego controlado por placebo com objetivo de avaliar a eficácia e a segurança da terapia com G-CSF com o uso concomitante de terapia padrão para IC em pacientes com CCC. MÉTODOS: Na Bahia, Brasil, foram incluídos 37 pacientes com cardiomiopatia chagásica, idade entre 20 e 75 anos, classe funcional II a IV da New York Heart Association (NYHA) e fração de ejeção do ventrículo esquerdo (FEVE) \2264 50%. Todos os pacientes receberam tratamento padrão para IC por dois meses antes da randomização para o grupo G-CSF (10 mcg / kg / dia) ou placebo, ambos associados a manutenção do tratamento para IC. O desfecho primário foi a estabilização ou melhora da classe funcional desde o início até 6 e 12 meses após o tratamento. A análise estatística foi por intenção de tratar. RESULTADOS: As características basais dos pacientes foram bem equilibradas entre os grupos. A maioria dos pacientes apresentava insuficiência cardíaca em classe II da NYHA (86,4%) e, em ambos os grupos, uma média baixa de FEVE (32% ± 7 no grupo G-CSF e 33% ± 10 no grupo placebo). A frequência do desfecho primário em 6 meses foi de 78% vs 66% (p: 0,47) e aos 12 meses foi de 68% vs 72% (p: 0,80) nos grupos placebo e G-CSF, respectivamente. Em relação ao perfil de segurança, o G-CSF foi seguro, sem qualquer adverso grave relacionado ao tratamento teste e nenhuma diferença na mortalidade em comparação com o grupo placebo. Embora a análise exploratória dos desfechos secundários não tenha sido estatisticamente significativa, o consumo máximo de oxigênio (VO2 máx) mostrou uma tendência de melhora no grupo G-CSF aos 12 meses. CONCLUSÃO: A terapia com G-CSF no CCC é segura e bem tolerada, porém sua eficácia na prevenção da progressão dos sintomas não pôde ser demonstrada pelo presente estudo.

Assessment of speckle tracking strain predictive value for myocardial fibrosis in subjects with Chagas disease.

BACKGROUND: One of the most challenging issues of chronic Chagas disease is to provide earlier detection of heart involvement. Two-dimensional speckle tracking (2-D ST) echocardiography, a new imaging modality with useful applications in several cardiac diseases, has been validated for subjects with myocardial infarction against cardiac magnetic resonance (CMR). Here we hypothesize that the longitudinal global strain (LGS) has an incremental value to ejection fraction for predicting myocardial fibrosis in subjects with Chagas disease. METHODS: This observational study comprised 58 subjects with Chagas disease, confirmed by two positive serologic tests. All subjects underwent conventional Doppler echocardiogram plus speckle tracking strain, and cardiac magnetic resonance. RESULTS: The ROC curve analysis revealed that both LGS (area under the curve: 0.78, p = 0.001) and ejection fraction (area under the curve: 0.82, p < 0.001) were significant predictors of myocardial fibrosis. Regarding the percentage of fibrosis, a high correlation was observed with both ejection fraction assessed by echocardiography (r = 0.70, p < 0.001) and LGS (r = 0.64, p < 0.001). However, when adjusted through multiple linear regression, the LGS lost statistical significance as a predictor of myocardial fibrosis (p = 0.111). CONCLUSIONS: LGS has no incremental value to conventional ejection fraction measurement in the prediction of myocardial fibrosis in subjects with Chagas disease.

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease / Avaliação do Polimorfismo da Galectina-3 em Indivíduos com Doença de Chagas Crônica

AbstractBackground:Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated.Objective:The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.Methods:Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.Results:For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease.Conclusion:Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0).

ResumoFundamento:A galectina-3, uma lectina de ligação à β-galactosidase, foi descrita como um mediador de fibrose cardíaca em estudos experimentais e um fator de risco associado com eventos cardiovasculares em indivíduos com insuficiência cardíaca. Estudos prévios avaliaram a susceptibilidade genética para doença de Chagas em humanos, incluindo polimorfismos dos genes de citocinas, demonstrando correlações entre o polimorfismo genético e o desenvolvimento de cardiomiopatia na fase crônica. No entanto, a relação entre polimorfismos de nucleotídeo único (single nucleotide polymorphism, SNP) e variações fenotípicas na doença de Chagas ainda não foi avaliada.Objetivo:O presente estudo teve como objetivo determinar se os polimorfismos genéticos da galectina-3 podem predispor ao desenvolvimento de formas cardíacas da doença de Chagas.Métodos:Cinquenta e cinco indivíduos com doença de Chagas foram incluídos neste estudo observacional. A genotipagem das variantes rs4644 e rs4652 do gene da galectina-3 foi realizada por PCR (reação em cadeia de polimerase).Resultados:Para o SNP rs4644, não houve associação entre o risco relativo para a forma cardíaca e os genótipos AA (OR = 0,79, p = 0,759), AC (OR = 4,38, p = 0,058), ou CC (OR = 0,39, p = 0,127). Similarmente, para o SNP rs4652, não foi encontrada associação entre os genótipos AA (OR = 0,64, p = 0,571), AC (OR = 2,85, p = 0,105), ou CC (OR = 0,49, p = 0,227) e a forma cardíaca da doença.Conclusão:Nossos resultados não mostraram associação entre os diferentes genótipos para ambos SNPs do gene da galectina-3 e a forma cardíaca da doença de Chagas. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0).