Detection of myocardial inflammation in Chagas\' heart disease by cardiac magnetic resonance

INTRODUÇÃO: A cardiopatia chagásica (CC) é um importante problema de saúde pública na América do Sul e a patogênese desta doença ainda não é totalmente compreendida, mas a inflamação e a fibrose miocárdica participam de forma central no processo crônico e progressivo de dano miocárdico. Trabalho prévio de nosso grupo demonstrou a capacidade da Ressonância Magnética Cardiovascular (RMC) de identificar precisamente a fibrose miocárdica em pacientes com Doença de Chagas. A RMC demonstrou ser eficaz para avaliar edema miocárdico, como marcador de inflamação, e ser altamente sensível para a detecção de trombos intracavitários, especialmente no ventrículo esquerdo, e em outras patologias, como miocardites e infartos. A avaliação de edema miocárdio pela RMC em pacientes com CC não foi ainda avaliada na literatura. Nosso objetivo foi investigar a presença de edema e fibrose miocárdica nas três formas clínicas da CC, o que julgamos ser de potencial valor diagnóstico e prognóstico. MÉTODOS: Cinquenta e quatro pacientes com doença de chagas foram analisados: 16 pacientes com a forma indeterminada (FI), 17 pacientes com CC-SD e 21 pacientes com CC-CD. Todos os pacientes foram submetidos a exame de RMC em equipamento de 1,5 T, utilizando a sequência de realce tardio do miocárdio (RTM), a sequência de edema miocárdico (Spin-eco ponderado em T2) e a sequência de realce global precoce ponderado T1 pós-contraste, para identificar fibrose, edema e hiperemia miocárdicos, respectivamente. RESULTADOS: A fibrose miocárdica foi encontrada em 39 indivíduos, 72,2% de toda a amostra. A fibrose miocárdica foi detectada em 2 pacientes (12,5%) na forma indeterminada, com uma massa de fibrose média de 0,85 ± 2,47g. Os pacientes da forma CC-SD em sua quase totalidade - 16 pacientes (94,1%) - apresentaram fibrose, com uma massa média de 13,0 ± 10,8g. Todos os pacientes com a forma CC-CD apresentaram fibrose miocárdica (21 pacientes) e adicionalmente detinham a maior massa de fibrose média, 25 ± 11,9g. O edema miocárdico foi encontrado em 40 indivíduos, 74,0% de toda a amostra. A extensão do edema miocárdico foi analisada pelo número de segmentos comprometidos. Foram identificados 3 pacientes (18,8%) da forma indeterminada com critérios positivos para edema miocárdio, determinando uma média de 0,31 ± 0,87 segmentos. A forma CC-SD obteve a presença de edema em 16 indivíduos (94,1%) distribuídos em uma média de 3,24 ± 2,3 segmentos. Todos os pacientes da forma CC-CD apresentaram edema miocárdico pela RMC, em uma média 3,67 ± 1,82 segmentos (p < 0,001). Houve correlação significativa entre a quantidade de fibrose miocárdica e edema miocárdico com a gravidade das formas clínicas (p < 0,001), classe funcional (p < 0,001), fração de ejeção do VE (p < 0,001) e volume diastólico do VE(p < 0,001). CONCLUSÃO: Fibrose e inflamação miocárdica foram detectadas pela ressonância magnética cardíaca em pacientes portadores de cardiopatia chagásica em todas as fases crônicas da doença, inclusive naqueles pacientes sem cardiopatia ou com cardiopatia sem disfunção ventricular. A quantidade de fibrose e edema miocárdico apresenta correlação com a gravidade da forma clínica, classe funcional, fração de ejeção do VE e dilatação do VEBACKGROUND AND PURPOSE: Chagas\' heart disease (CHD) is a major public health problem in South America, and the pathogenesis of this disease is not yet fully understood, but inflammation and myocardial fibrosis seem to play a central role in the process of chronic and progressive myocardial damage. Previous descriptions from our group demonstrated the ability of Cardiovascular Magnetic Resonance (CMR) accurately identify myocardial fibrosis in patients with CHD. CMR shown to be effective for assessing myocardial edema, a marker of inflammation, and is highly sensitive for the detection of thrombi, especially in the left ventricle in other pathologies such as myocarditis and myocardial infarct. The assessment of myocardial edema by CMR in patients with CHD has not been evaluated. We believe to be of potential diagnostic and prognostic value to investigate the presence of myocardial edema and fibrosis in patients in the three clinical forms of this disease. METHODS: Fifty-four patients with Chagas\' disease were analyzed: 16 patients with the indeterminate phase (IF), 17 patients with the cardiac form without left ventricular systolic dysfunction (CFWO), and 21 patients with the cardiac form with left ventricular systolic dysfunctional form (CFSD). All patients underwent 1.5-T cardiac magnetic resonance (CMR) using the myocardial delayed enhancement sequence (MDE), T2-weighted sequence and the T1 weighted global enhancement after contrast sequence, to identify fibrosis, edema and hyperemia, respectively. RESULTS: Myocardial fibrosis was found in 39 subjects, 72.2% of the entire sample. Myocardial fibrosis was detected in 2 patients (12.5%) with the indeterminate form, representing an average mass of fibrosis of 0.85 ± 2.47 g. Patients with the CFWO almost entirely, 16 patients (94.1%) showed fibrosis, representing an average mass of fibrosis of 13.0 ± 10.8 g. All patients with the CFSD had myocardial fibrosis (21 patients) additionally had greater average mass of fibrosis 11.9 ± 25g. The myocardial edema was found in 40 subjects, 74.0% of the entire sample. The extent of myocardial edema was determined by the number of segments affected. We identified three patients (18.8%) from the indeterminate form with myocardial edema, an average of 0.31 ± 0.87. The CFWO presented a high presence of edema in 16 individuals (94.1%) distributed in an average of 3.24 ± 2.3 segments. All patients with the CFSD presented myocardial edema, an average of 3.67 ± 1.82 segments. (p < 0.001). There was significant correlation between the amount of myocardial fibrosis and myocardial edema with the severity of the clinical forms ( p < 0.001 ), functional class ( p < 0.001 ), LV ejection fraction ( p < 0.001 ) and left ventricular diastolic volume ( p < 0.001). CONCLUSION: Myocardial fibrosis and inflammation were detected by cardiac magnetic resonance imaging in patients with Chagas\' disease in all stages of chronic disease, including those patients without heart disease or cardiomyopathy without ventricular dysfunction. The amount of fibrosis and myocardial edema correlates with the severity of the clinical, functional class, LV ejection fraction and LV dilatio

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

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-12T12:36:51Z No. of bitstreams: 1 Macedo CT Assessment....pdf: 661652 bytes, checksum: a14aaf455b6a4c89eef253f8b95079bc (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-12T12:51:06Z (GMT) No. of bitstreams: 1 Macedo CT Assessment....pdf: 661652 bytes, checksum: a14aaf455b6a4c89eef253f8b95079bc (MD5)Made available in DSpace on 2016-05-12T12:51:06Z (GMT). No. of bitstreams: 1 Macedo CT Assessment....pdf: 661652 bytes, checksum: a14aaf455b6a4c89eef253f8b95079bc (MD5) Previous issue date: 2015Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilBackground: 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 imagingmodalitywith 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 subjectswith Chagas disease, confirmed by two positive serologic tests. All subjects underwent conventional Doppler echocardiogramplus speckle tracking strain, and cardiacmagnetic 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 b 0.001)were significant predictors ofmyocardial fibrosis. Regarding the percentage of fibrosis, a high correlation was observed with both ejection fraction assessed by echocardiography (r =0.70, p b 0.001) and LGS (r = 0.64, p b 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 fractionmeasurement in the prediction ofmyocardial fibrosis in subjects with Chagas disease

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

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-23T13:16:57Z No. of bitstreams: 1 Cruz GS Assessment....pdf: 409829 bytes, checksum: 769c74faa40f7a24344a6dc548381ea6 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-23T13:35:11Z (GMT) No. of bitstreams: 1 Cruz GS Assessment....pdf: 409829 bytes, checksum: 769c74faa40f7a24344a6dc548381ea6 (MD5)Made available in DSpace on 2016-03-23T13:35:11Z (GMT). No. of bitstreams: 1 Cruz GS Assessment....pdf: 409829 bytes, checksum: 769c74faa40f7a24344a6dc548381ea6 (MD5) Previous issue date: 2015Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Hospital São Rafael. Departamento de Cardiologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Departamento de Cardiologia. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilBACKGROUND: 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

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

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-11-23T12:50:45Z No. of bitstreams: 1 Rabelo MMN Evaluation of galectin-3....pdf: 140623 bytes, checksum: 3f19bd9f18869f4e4c812b28c9829fdf (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-11-23T13:01:55Z (GMT) No. of bitstreams: 1 Rabelo MMN Evaluation of galectin-3....pdf: 140623 bytes, checksum: 3f19bd9f18869f4e4c812b28c9829fdf (MD5)Made available in DSpace on 2017-11-23T13:01:55Z (GMT). No. of bitstreams: 1 Rabelo MMN Evaluation of galectin-3....pdf: 140623 bytes, checksum: 3f19bd9f18869f4e4c812b28c9829fdf (MD5) Previous issue date: 2017FAPESBHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Clinical Diagnostics Laboratory. Salvador, BA, BrasilHospital São Rafael. Clinical Diagnostics Laboratory. Salvador, BA, BrasilCenter for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilChagas 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 diseas

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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div

Correlation between LVEF and serum concentration of syndecan-4 and NT-ProBNP.

<p>A: Pearson’s correlation, LVEF assessed by Simpson’s method, r = 0.02, P = 0.864. B = Pearson’s correlation, LVEF assessed by Simpson’s method, r = 0.687, P<0.001.</p

Correlation between percentage of myocardial fibrosis assessed by cardiovascular MRI and concentration of syndecan-4 and NT-ProBNP.

<p>A: Pearson’s correlation, r = 0.08, P = 0.567. B: Pearson’s correlation, r = 0.469, P<0.001.</p