ABSTRACT The present study aimed to establish a population pharmacokinetic (PopPK) modeling of benznidazole (BZD) in Brazilian patients with chronic Chagas disease. This was part of a Brazilian prospective cohort study with eight patients diagnosed with Chagas disease during the beginning of BZD treatment up to the 60th day. On the 15th day of treatment, a blood sampling was collected and analyzed. A one-compartment PK model was developed using Pmetrics. Patients with an average age of 50.3 (SD: 6.2) years old, 6 female patients and 2 males, 70.2 kg (14.2), receiving a 5 mg/Kg/day dose were included. PK parameters estimated for CL, V and Ka were 6.27 L/h, 38.97 L and 1.66 h-1, respectively. This is the first study to establish a population pharmacokinetic modeling of BZD in Brazilian patients with chronic Chagas disease. Therefore, further studies are needed to obtain the complete characterization of BZD pharmacokinetics.

Resumo Fundamento As características histopatológicas da doença de Chagas (DCC) são: presença de miocardite, destruição das fibras cardíacas e fibrose miocárdica. A Galectina-3 (Gal-3) é um biomarcador envolvido no mecanismo de fibrose e inflamação que pode ser útil para a estratificação de indivíduos com DCC por risco. Objetivos Nosso objetivo foi avaliar se níveis elevados de Gal-3 estão associados a formas graves de cardiomiopatia chagásica (CC) e são preditivos de mortalidade. Métodos Estudamos doadores de sangue (DS) positivos para anti-T. cruzi: não-CC-DS (187 DS sem CC com eletrocardiograma [ECG] e fração de ejeção do ventrículo esquerdo [FEVE] normais); CC-Não-Dis-DS (46 DS com CC e apresentando ECG anormal, mas FEVE normal); e 153 controles negativos correspondentes. Esta amostra foi composta por 97 pacientes com CC grave (CC-Dis). Usamos as correlações de Kruskall-Wallis e Spearman para testar a hipótese de associações, assumindo um p bicaudal <0,05 como significativo. Resultados O nível de Gal-3 foi de 12,3 ng/mL para não-CC-DS, 12,0 ng/mL para CC-Não-Dis-DS, 13,8 ng/mL para controles e 15,4 ng/mL para CC-Dis. FEVE <50 foi associada a níveis mais elevados de Gal-3 (p=0,0001). Em nosso modelo de regressão linear ajustado, encontramos associação entre os níveis de Gal-3 e os parâmetros do ecocardiograma em indivíduos positivos para T. cruzi. Nos pacientes CC-Dis, encontramos uma associação significativa de níveis mais elevados de Gal-3 (≥15,3 ng/mL) e morte ou transplante cardíaco em acompanhamento de cinco anos (Hazard ratio – HR 3,11; IC95% 1,21– 8,04; p=0,019). Conclusões Em pacientes com CC, níveis mais elevados de Gal-3 estiveram significativamente associados a formas graves da doença e maior taxa de mortalidade em longo prazo, o que significa que pode ser um meio efetivo para identificar pacientes de alto risco. (Arq Bras Cardiol. 2021; 116(2):248-256)

Abstract Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD. Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality. Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman’s correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant. Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio – HR 3.11; 95%CI 1.21–8.04; p=0.019). Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)

Resumo Fundamento A galectina-3 (Gal-3) é uma molécula pró-inflamatória e pró-fibrótica, envolvida na patogênese da insuficiência cardíaca. O papel da Gal-3 em pacientes com pericardite constritiva crônica (PCC) não está claro. Objetivo O objetivo deste estudo foi avaliar os níveis de Gal-3 em pacientes com PCC e correlacioná-los com parâmetros clínicos, funcionais e histológicos. Métodos Nós avaliamos prospectivamente 25 pacientes sintomáticos com PCC agendados à pericardiectomia e 21 controles sadios. Os pacientes foram submetidos à avaliação clínica, medidas de Gal-3 e peptídeo natriurético do tipo B (BNP), ecocardiografia, ressonância magnética cardíaca e teste cardiopulmonar de exercício (TCPE) no período basal. Seis meses após a pericardiectomia, repetiu-se o TCPE. Um erro alfa < 5% foi considerado estatisticamente significativo, com um intervalo de confiança de 95%. Resultados Foram incluídos 25 pacientes com idade mediana de 45 anos. A etiologia foi principalmente idiopática (n = 19, 76%), e 14 (56%) apresentaram classe funcional New York Heart Association (NYHA) III/IV. Os valores medianos de BNP e Gal-3 foram 143 (89-209) pg/dL e 14,8 (9,7-17,2) ng/mL, respectivamente. Os níveis de Gal-3 não foram estatisticamente maiores nos pacientes com PCC que em controles (p = 0,22). Não foram encontradas correlações significativas da Gal-3 com BNP, medidas ecocardiográficas e de ressonância magnética cardíaca, e achados histológicos. Após a pericardiectomia, encontrou-se uma correlação estatisticamente significativa entre Gal-3 e medidas do TCPE – duração do teste (r = –0,79; p < 0,001) e tempo de exercício (r = –0,79; p < 0,001). Conclusões Pacientes com PCC apresentaram níveis normais de Gal-3, quando comparados aos indivíduos controles. A Gal-3 não se correlacionou com medidas morfológicas e funcionais antes da pericardiectomia. No entanto, associações entre Gal-3 e intolerância ao exercício após pericardiectomia pode sugerir um papel da Gal-3 na predição de prognóstico após a pericardiectomia. (Arq Bras Cardiol. 2020; 114(4):683-689)

Abstract Background Galectin-3 (Gal-3) is a proinflammatory, profibrotic molecule implicated in the pathogenesis of heart failure. The role of Gal-3 in patients with chronic constrictive pericarditis (CCP) is not clear. Objective The aim of this study was to assess plasma Gal-3 in patients with CCP and correlate it with clinical, functional and histologic parameters. Methods We prospectively evaluated 25 symptomatic patients with CCP referred for pericardiectomy and 21 healthy controls. Patients underwent clinical assessment, Gal-3 and B-type natriuretic peptide (BNP) measurements, echocardiography, cardiac magnetic resonance imaging and cardiopulmonary exercise test (CPET) at baseline. Six months after pericardiectomy CPET was repeated. An alpha error < 5% was considered statistically significant, with a confidence interval of 95%. Results Twenty-five patients with a median age of 45 years were included. Etiology was mainly idiopathic (n = 19, 76%); and 14 (56%) patients had NYHA functional class III/IV. Median BNP and Gal-3 were 143 (89-209) pg/dL and 14.8 (9.7-17.2) ng/mL, respectively. Gal-3 levels were not significantly higher in CCP patients than in control (p = 0.22). There were no significant correlations of Gal-3 with BNP, echocardiographic and cardiac magnetic resonance measures and histological findings. After pericardiectomy, it was found a statistically significant correlation between Gal-3 and the CPTE measures test duration (r = –0.79; p < 0.001) and exercise time (r = –0.79; p < 0.001). Conclusions Patients with CCP had normal levels of Gal-3 as compared to the controls. Gal-3 did not correlate with morphological and functional measures before pericardiectomy. However, the associations between Gal-3 and exercise intolerance after pericardiectomy may suggest a role of Gal-3 in prognosis prediction after pericardiectomy. (Arq Bras Cardiol. 2020; 114(4):683-689)

Abstract Background: Galectin-3 is the designation given to the protein that binds to ß-galactosides, expressed by activated macrophages and described as a cardiac fibrosis mediator. In hypertrophic cardiomyopathy (HCM), myocardial fibrosis is an independent predictor of adverse outcome; however, the association between Galectin-3 and myocardial fibrosis has not been studied in this cardiopathy. Objective: To evaluate the association of Galectin-3 and the presence of myocardial fibrosis in a patient with hypertrophic cardiomyopathy. Methods: Galectin-3 was measured in automated equipment using the Elisa technique in 100 participants divided into two groups: 50 patients with hypertrophic cardiomyopathy and 50 healthy control subjects. All patients with hypertrophic cardiomyopathy underwent magnetic nuclear resonance with the late enhancement technique to investigate myocardial fibrosis. For the statistical analysis, p values < 0.05 were considered statistically significant. Results: Galectin-3 levels were low and did not show significant differences between patients with hypertrophic cardiomyopathy and the control group, 10.3 ± 3.1 ng/dL and 11.3 ± 2.6 ng/dL (p = 0.12) respectively. Myocardial fibrosis was a common finding and was identified in 84% (42/50) of patients with HCM, but no differences were observed between Galectin-3 levels when comparing patients with and without fibrosis, 10.3 ± 2.4 ng/dL and 10.1 ± 2.1 ng/dL (p = 0.59). Conclusion: The results did not show an association between Galectin-3 and myocardial fibrosis in patients with hypertrophic cardiomyopathy, suggesting that non-inflammatory mechanisms of myocardial fibrosis formation and cardiac remodeling are involved in this cardiopathy.

Abstract Visceral leishmaniasis is common in Brazil and is caused by Leishmania (Leishmania) infantum/chagasi. Post-kala-azar dermal leishmaniasis frequently follows visceral leishmaniasis caused by L. donovani, and para-kala-azar dermal leishmaniasis refers to an uncommon presentation wherein it occurs simultaneously along with visceral leishmaniasis. While post-kala-azar dermal leishmaniasis only occurs occasionally in L. infantum/chagasi infections, it frequently occurs in patients with concomitant immunosuppression (HIV co-infection). Here, we describe the first case of para-kala-azar dermal leishmaniasis in Brazil. It is important to raise awareness of post- and para-kala-azar dermal leishmaniasis in L. infantum endemic areas as these patients may contribute to visceral leishmaniasis transmission.

Resumo Fundamento: Estudos internacionais têm relatado o valor de perfil clínico e exames de imagem no diagnóstico e prognóstico da pericardite constritiva. Entretanto, dados da população brasileira são escassos. Objetivo: Avaliar as características clínicas, sensibilidade de exames de imagem e fatores relacionados ao óbito em uma série de casos de pericardite constritiva submetidos à pericardiectomia. Métodos: Pacientes com pericardite constritiva confirmada por cirurgia foram avaliados retrospectivamente quanto a variáveis clínicas e laboratoriais. Dois métodos diagnósticos foram utilizados: ecocardiograma transtorácico e ressonância cardíaca. Preditores de mortalidade foram determinados por análise univariada usando metodologia das proporções de Cox e hazard ratio. Todos os testes foram considerados bicaudais e um erro alfa ≤ 5% foi considerado como significante. Resultados: Foram estudados 84 pacientes com idade média de 44 ± 17,9 anos, sendo 67% do sexo masculino. Sinais e sintomas de insuficiência cardíaca (IC) predominantemente direita estiveram presentes com estase jugular, edema e ascite em 89%, 89% e 62% dos casos, respectivamente. Etiologia idiopática foi observada em 69% dos casos, seguida por tuberculose em 21%. Apesar do grau de IC, encontramos baixos níveis de BNP (mediana de 157 pg/mL). As sensibilidades diagnósticas para constrição do ecocardiograma e da ressonância foram 53,6% e 95,9%, respectivamente. Durante a evolução clínica, houve 9 óbitos (10,7%) e os fatores de risco foram: anemia, elevações de BNP, PCR, hipertensão pulmonar > 55 mmHg e fibrilação atrial. Conclusões: Pericardite constritiva manifesta-se com sinais e sintomas de IC biventricular com predomínio à direita e baixos níveis de BNP. A ressonância magnética apresenta melhor sensibilidade para diagnóstico. Marcadores clínicos, laboratoriais e de imagem estiveram associados ao óbito.

Abstract Background: International studies have reported the value of the clinical profile and laboratory findings in the diagnosis of constrictive pericarditis. However, Brazilian population data are scarce. Objective: To assess the clinical characteristics, sensitivity of imaging tests and factors related to the death of patients with constrictive pericarditis undergoing pericardiectomy. Methods: Patients with constrictive pericarditis surgically confirmed were retrospectively assessed regarding their clinical and laboratory variables. Two methods were used: transthoracic echocardiography and cardiac magnetic resonance imaging. Mortality predictors were determined by use of univariate analysis with Cox proportional hazards model and hazard ratio. All tests were two-tailed, and an alpha error ≤ 5% was considered statically significant. Results: We studied 84 patients (mean age, 44 ± 17.9 years; 67% male). Signs and symptoms of predominantly right heart failure were present with jugular venous distention, edema and ascites in 89%, 89% and 62% of the cases, respectively. Idiopathic etiology was present in 69.1%, followed by tuberculosis (21%). Despite the advanced heart failure degree, low BNP levels (median, 157 pg/mL) were found. The diagnostic sensitivities for constriction of echocardiography and magnetic resonance imaging were 53.6% and 95.9%, respectively. There were 9 deaths (10.7%), and the risk factors were: anemia, BNP and C reactive protein levels, pulmonary hypertension >55 mm Hg, and atrial fibrillation. Conclusions: Magnetic resonance imaging had better diagnostic sensitivity. Clinical, laboratory and imaging markers were associated with death.