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1.
Rev Soc Bras Med Trop ; 53: e20200100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32638887

RESUMO

Patients with Chagas cardiomyopathy (ChC) usually progress with fatigue and dyspnea. Exercise tests are valuable for the functional evaluation of these patients. However, information about the applicability of the exercise tests is scattered, and no studies have systematically reviewed the results. Thus, the present review explored the general aspects and prognostic value of exercise tests in patients with ChC. A literature search of the MEDLINE, Web of Science, CINAHL, Scopus, and LILACS databases was performed to identify relevant studies. There were no data restrictions, and articles that met the objective of the study were selected. Articles written in English, Portuguese, and Spanish were considered, and 25 articles were finally included. The peak oxygen uptake (VO2peak) was correlated with demographic and echocardiographic variables. Echocardiographic features of the left ventricular diastolic function and right ventricular systolic function appeared to be determinants of functional capacity, in addition to age and sex. VO2peak was associated with higher mortality, especially in patients with dilated ChC. The minute ventilation/carbon dioxide production slope (VE/VCO2 slope) was a strong predictor of survival; however, more studies are needed to verify this observation. Field tests showed moderate to strong correlation with VO2peak and thus may be inexpensive tools for the functional evaluation of patients with ChC. However, few studies have verified their prognostic significance. While exercise tests are useful tools for functional assessment, information is scarce regarding further considerations, and many of the criteria are based on guidelines for other heart diseases.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Teste de Esforço/métodos , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/fisiopatologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Ecocardiografia , Humanos , Prognóstico
2.
Int J Cardiovasc Imaging ; 36(11): 2209-2219, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32613382

RESUMO

Chagas' disease (CD), caused by the parasite Trypanosoma cruzi, is the leading cause of cardiac disability from infectious diseases in Central and South America. The disease progresses through an extended, asymptomatic form characterized by latency without clinical manifestations into a symptomatic form with cardiac and gastro-intestinal manifestations. In the terminal phase, chronic Chagas' myocarditis results in extensive myocardial fibrosis, chamber enlargement with aneurysms and ventricular tachycardia (VT). Cardiac magnetic resonance imaging (CMR) has proven useful in characterizing myocardial fibrosis (MF). Sub-epicardial and mid-wall fibrosis are less common patterns of MF in CHD than transmural scar, which resembles myocardial infarction. Commonly involved areas of MF include the left ventricular apex and basal infero-lateral wall, suggesting a role for watershed ischemia in the pathophysiology of MF. Electrophysiology studies have helped refine the relationship between MF and VT in this setting. This article reviews the patterns of MF in CHD and correlate these patterns with electrogram patterns to predict risk of ventricular arrhythmias and sudden death.


Assuntos
Potenciais de Ação , Cardiomiopatia Chagásica/diagnóstico por imagem , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Imagem por Ressonância Magnética , Miocárdio/patologia , Taquicardia Ventricular/diagnóstico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/fisiopatologia , Progressão da Doença , Fibrose , Sistema de Condução Cardíaco/parasitologia , Humanos , Valor Preditivo dos Testes , Taquicardia Ventricular/parasitologia , Taquicardia Ventricular/fisiopatologia
3.
Am J Trop Med Hyg ; 103(2): 745-751, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32431281

RESUMO

Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease (n = 47) and a control group (n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) was performed. There was an increase in myocardial fibrosis CMR parameters and ventricular arrhythmias among different stages of Chagas disease, combined with a decrease in the left ventricular ejection fraction (LVEF) by CMR and also in the right ventricular systolic function by S' wave on tissue Doppler. Fibrosis mass and ECV were associated with the Rassi score, ventricular extrasystole, and E/e' ratio in a logistic regression model adjusted for age and gender. The ECV maintained an association with the presence of NSVT, even after adjustments for fibrosis mass and LVEF assessed by CMR. The receiver-operating characteristic area under the curve for global ECV (0.85; 95% CI: 0.71-0.99) and NSVT was greater than that for fibrosis mass (0.75; 95% CI: 0.54-0.96), although this difference was not statistically significant. Extracellular volume could be an early marker of increased risk of ventricular arrhythmia in Chagas disease, presenting an independent association with NSVT in the initial stages of chronic Chagas cardiomyopathy, even after adjustment for fibrosis mass and LVEF.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Coração/diagnóstico por imagem , Taquicardia Ventricular/fisiopatologia , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/diagnóstico por imagem , Doença de Chagas/complicações , Doença de Chagas/diagnóstico por imagem , Doença de Chagas/fisiopatologia , Estudos Transversais , Ecocardiografia , Eletrocardiografia Ambulatorial , Espaço Extracelular , Feminino , Fibrose , Humanos , Modelos Logísticos , Imagem por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Tamanho do Órgão , Curva ROC , Volume Sistólico , Taquicardia Ventricular/etiologia , Função Ventricular Direita
4.
Am J Cardiol ; 125(9): 1413-1420, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171439

RESUMO

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


Assuntos
Cardiomiopatia Chagásica/terapia , Exercício Físico , Idoso , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/fisiopatologia , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
5.
PLoS Pathog ; 16(3): e1008379, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32160269

RESUMO

Chagas Disease (CD) is one of the leading causes of heart failure and sudden death in Latin America. Treatments with antioxidants have provided promising alternatives to ameliorate CD. However, the specific roles of major reactive oxygen species (ROS) sources, including NADPH-oxidase 2 (NOX2), mitochondrial-derived ROS and nitric oxide (NO) in the progression or resolution of CD are yet to be elucidated. We used C57BL/6 (WT) and a gp91PHOX knockout mice (PHOX-/-), lacking functional NOX2, to investigate the effects of ablation of NOX2-derived ROS production on the outcome of acute chagasic cardiomyopathy. Infected PHOX-/- cardiomyocytes displayed an overall pro-arrhythmic phenotype, notably with higher arrhythmia incidence on ECG that was followed by higher number of early afterdepolarizations (EAD) and 2.5-fold increase in action potential (AP) duration alternans, compared to AP from infected WT mice. Furthermore, infected PHOX-/- cardiomyocytes display increased diastolic [Ca2+], aberrant Ca2+ transient and reduced Ca2+ transient amplitude. Cardiomyocyte contraction is reduced in infected WT and PHOX-/- mice, to a similar extent. Nevertheless, only infected PHOX-/- isolated cardiomyocytes displayed significant increase in non-triggered extra contractions (appearing in ~75% of cells). Electro-mechanical remodeling of infected PHOX-/-cardiomyocytes is associated with increase in NO and mitochondria-derived ROS production. Notably, EADs, AP duration alternans and in vivo arrhythmias were reverted by pre-incubation with nitric oxide synthase inhibitor L-NAME. Overall our data show for the first time that lack of NOX2-derived ROS promoted a pro-arrhythmic phenotype in the heart, in which the crosstalk between ROS and NO could play an important role in regulating cardiomyocyte electro-mechanical function during acute CD. Future studies designed to evaluate the potential role of NOX2-derived ROS in the chronic phase of CD could open new and more specific therapeutic strategies to treat CD and prevent deaths due to heart complications.


Assuntos
Arritmias Cardíacas/metabolismo , Sinalização do Cálcio , Cardiomiopatia Chagásica/metabolismo , Miócitos Cardíacos/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doença Aguda , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Cálcio/metabolismo , Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Knockout , Miócitos Cardíacos/patologia , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo
7.
J Cardiovasc Electrophysiol ; 30(11): 2370-2376, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506997

RESUMO

BACKGROUND: Variability of ventricular arrhythmias among days in patients with Chagas disease is not detected by 24 hours of Holter monitoring. OBJECTIVE: To analyze whether ventricular arrhythmias are a random phenomenon or have a reproducible behavior in patients with Chagas cardiomyopathy. METHOD: Holter monitoring was recorded in 16 subjects with a mean age of 52 ± 8 years. They were clinically stable and had ventricular couplets, isolated premature ventricular contractions (PVCs), and nonsustained ventricular tachycardia (NSVT). The recordings occurred for 7 days. Hurst exponent (HE) evaluated randomness and predictability index (PI) and repeated analysis of variance (ANOVA) assessed reproducibility. RESULTS: The HE was significantly greater than 0.5 in all 16 patients, which confirms the nonrandomness of arrhythmias in this Chagas sample. The PI for ventricular couplets and isolated PVCs was, on average, 38% and 54%, respectively. ANOVA with repeated measurement showed significant differences in the daily frequency of ventricular couplets (n = 15, P ≤ .05), isolated PVC (n = 12, P ≤ .05), and NSVT (n = 7, P ≤ .05). CONCLUSION: Ventricular arrhythmias in Chagas cardiomyopathy are not random. Dissimilarities in arrhythmias frequency make unlikely that 24 hours of Holter recording can capture this variability.


Assuntos
Cardiomiopatia Chagásica/complicações , Eletrocardiografia Ambulatorial , Frequência Cardíaca , Periodicidade , Taquicardia Ventricular/diagnóstico , Complexos Ventriculares Prematuros/diagnóstico , Potenciais de Ação , Adulto , Idoso , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Complexos Ventriculares Prematuros/etiologia , Complexos Ventriculares Prematuros/fisiopatologia
8.
J Cardiovasc Electrophysiol ; 30(11): 2448-2452, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31502385

RESUMO

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


Assuntos
Cardiomiopatia Chagásica/terapia , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Insuficiência Cardíaca/terapia , Prevenção Secundária/instrumentação , Adulto , Idoso , Brasil/epidemiologia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
9.
PLoS One ; 14(8): e0221028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31437176

RESUMO

BACKGROUND: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis. OBJECTIVE: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients. METHODS: We enrolled 112 patients, age of 56.7 ± 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation. RESULTS: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035). CONCLUSIONS: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio.


Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Chagásica/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Adulto , Idoso , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Feminino , Seguimentos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico/fisiologia , Análise de Sobrevida , Função Ventricular Esquerda/fisiologia
10.
Catheter Cardiovasc Interv ; 94(4): 644-650, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334914

RESUMO

INTRODUCTION: Chagas disease is one of the most relevant endemic parasitic diseases in Latin America, affecting approximately 6 million people. Overt Chagas heart disease is an ominous condition, occurring in 20-30% of infected individuals, which has besides the persistent myocarditis a peculiar intracardiac ganglionic neuronal depletion and dysautonomy. This study aims to evaluate the safety and feasibility of renal denervation for patients with advanced symptomatic Chagas cardiomyopathy. METHODS: Open-label prospective pilot study that randomized patients with Chagas heart disease to either renal denervation or conservative treatment (2:1 ratio). The primary endpoint was the incidence of major adverse events at 9 months, defined as a composite of all-cause death, myocardial infarction, stroke, need for renal artery invasive treatment, or worsening renal function. RESULTS: A total of 17 patients were allocated for renal denervation (n = 11) or conservative treatment (n = 6). Included patients had severe symptomatic heart disease, with markedly depressed left ventricular function (average ejection fraction 26.7 ± 4.9%). For patients randomized to renal denervation, the procedure was performed successfully and uneventfully. After 9 months, the primary endpoint occurred in 36.4% of patients in the renal denervation group and 50.0% in the control arm (p = .6). After 9 months, clinical, laboratory, functional, echocardiographic, and quality of life parameters were similar between groups. CONCLUSIONS: This pilot study suggests that renal denervation is safe and feasible in patients with Chagas cardiomyopathy, warranting future studies to better evaluate the clinical efficacy of the interventional strategy in improving the prognosis of this high-risk population.


Assuntos
Denervação Autônoma , Ablação por Cateter , Cardiomiopatia Chagásica/cirurgia , Insuficiência Cardíaca/cirurgia , Rim/inervação , Idoso , Denervação Autônoma/efeitos adversos , Denervação Autônoma/mortalidade , Brasil , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/parasitologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
11.
Parasite Immunol ; 41(10): e12663, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31309590

RESUMO

Chronic Chagas cardiomyopathy (CCC) is responsible for the disease's greater morbidity and poor prognosis. Although understanding the pathophysiology of CCC and the fundamentals of its clinical management derives from research related to other cardiomyopathies, there are peculiarities that distinguish CCC from the others. CCC is the most fibrous heart disease, and its myocardial involvement is important as it disorganizes or disrupts the extracellular matrix, creating an environment conducive to the formation of arrhythmogenic foci. It is also considered the most arrhythmogenic of the known heart diseases, giving rise to complex arrhythmias, usually associated with varying degrees of stimulus conduction disorders. The central proposal of this review is to describe a possible association between the distribution and degree of myocardial fibrosis and cardiac arrhythmogenicity in patients with Chagas cardiomyopathy, drawing attention to the importance of noninvasive biomarkers for the quantification of myocardial fibrosis.


Assuntos
Cardiomiopatia Chagásica/patologia , Miocárdio/patologia , Arritmias Cardíacas/patologia , Biomarcadores/análise , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Fibrose , Humanos , Necrose
12.
J Cardiovasc Electrophysiol ; 30(9): 1517-1525, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31172602

RESUMO

BACKGROUND: Ventricular tachycardia (VT) is one of the main predictors of mortality in Chagas cardiomyopathy (CC). Although the substrate of sustained and nonsustained-VT (NS-VT) seems to be the same, little is known about the distribution of late enhancement (LE). Our aim was to compare the clinical findings and the amount and patterns of LE in Chagas disease according to the presence and type of VT. METHODS AND RESULTS: Magnetic resonance imaging was performed in 54 Chagas seropositive patients: 8 indeterminate and 46 with CC of whom 15 were without VT, 13 with NS-VT, and 18 with sustained-VT (S-VT). There were 31 males (57%), mean age was 55.9 ± 12.2 years. LE was found in 87% of all patients and in 50%, 80%, and 100% of the indeterminate, without VT and VT groups, respectively. The percentage of LE increased progressively in the indeterminate, CC without VT, and CC with VT groups; without a significant difference between NS-VT and S-VT (0.93%, 15.2%, 23.2%, and 21.4%, respectively). The amount of LE increased with the functional class. LE in the basal and mid lateral wall was more frequent in VT, without difference between S-VT and NS-VT. The only predictor of VT was the percentage of LE, odds ratio (OR), 6.2; (95% confidence interval [CI], 3.7-28.4; P = .01) with a cutoff of Odds Ratio 17.1%. CONCLUSIONS: The amount of LE increases in relation to the clinical stage of the disease and its functional class in Chagas seropositive patients. The amount of LE was the main predictor of VT, without difference between S-VT and NS-VT.


Assuntos
Cardiomiopatia Chagásica/diagnóstico por imagem , Eletrocardiografia , Imagem Cinética por Ressonância Magnética , Taquicardia Ventricular/diagnóstico , Potenciais de Ação , Adulto , Idoso , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/fisiopatologia , Meios de Contraste/administração & dosagem , Feminino , Gadolínio DTPA/administração & dosagem , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Volume Sistólico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Função Ventricular Esquerda , Função Ventricular Direita
13.
Life Sci ; 230: 141-149, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129142

RESUMO

When administered alone, preinfection exercise training and benznidazole-based chemotherapy induce cardioprotection in Chagas disease. However, the effect of concomitant exercise and benznidazole treatment is unknown. We investigated whether exercise and specific chemotherapy could interact to modulate parasitemia, inflammation, redox status and heart damage in a murine model of T. cruzi infection. Wistar rats were randomized into an uninfected control group (CNT) and four groups infected with T. cruzi: sedentary untreated (SUN) and treated (STR), and trained untreated (TUN) and treated (TTR). Running training was administered 5 days/week for 4 weeks. Treated animals concomitantly received 100 mg/kg/day benznidazole. Heart inflammation and reactive damage were not detected in CNT animals. Compared to SUN, TUN animals presented increased levels of parasitemia, myocarditis, nitric oxide, hydrogen peroxide, protein carbonyl, malondialdehyde, cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10 and IL-17), catalase, superoxide dismutase and glutathione reductase activity, as well as reduced heart non-protein antioxidant levels (P < 0.05). TTR animals exhibited higher levels of parasitemia, myocarditis, hydrogen peroxide, malondialdehyde, IFN-γ, TNF-α and IL-6 than STR animals (P < 0.05), which showed the lowest levels of all analyzed parameters compared to the other groups (P < 0.05). Our findings indicate that exercise aggravates acute infection. When concomitantly administered with benznidazole, exercise training impaired parasitic control and chemotherapy-induced cardioprotection in T. cruzi-infected rats. Considering that exercise training and T. cruzi infection constitute independent metabolic challenges, the negative effects of concomitant treatment are potentially related to the overlapping oxidative and immunoinflammatory demands of exercise and the infection itself.


Assuntos
Doença de Chagas/tratamento farmacológico , Doença de Chagas/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Antioxidantes/farmacologia , Cardiotônicos/metabolismo , Catalase/metabolismo , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Citocinas/metabolismo , Modelos Animais de Doenças , Coração/fisiologia , Inflamação/metabolismo , Interleucina-10/metabolismo , Masculino , Miocardite/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Nitroimidazóis/farmacologia , Parasitemia/parasitologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/metabolismo
14.
Arq Bras Cardiol ; 112(2): 189-192, 2019 Feb.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30785584

RESUMO

Changes in iron metabolism in heart failure (HF) have been described as an important prognostic marker. To check if the markers of iron kinetics are related to the morbidity and etiology of chagasic cardiomyopathy. Patients with Chronic Chagasic Cardiomyopathy (CCC, n = 40), with indeterminate form (IND, n = 40), besides non-chagasic cardiomyopathy (NCh, n = 40). The mean age was 50.98 ± 5.88 in CCC, 50% were male, 49.68 ± 5.28 in IND, 52.2% were male, and 49.20 ± 10.09 in NCh, 12.5% were male. Lower levels of iron (FeSe) were observed in the CCC groups (93.15 ± 36.53), when compared to IND (125.30 ± 22.79) and NCh (114.77 ± 18.90) (p = 0.0004), lower IST transferrin saturation index in CCC (29.48 ± 6.59), when compared to IND (30.95 ± 7.06) and in the NCh group (39.70 ± 7.54) p = 0.0001), total binding capacity of the lower CTLF iron in the CCC group (297.30 ± 36.46), when compared to the IND group (196.52 ± 56.95) and the NCh group (275.18 ± 33, 48) (p = 0.0001), lower ferritin in the CCC group (134.55, 1.56-42.36), when compared to the IND group (156,25, 1,72-42,20) and the NCh group (112.95, 2.88-42.66) (p = 0.0004). It was also observed that FeSe (95% CI 1.00-1.04, p = 0.0014), IST (95% CI 1.02-1.22) (p = 0.0012) and gender (95% CI 1.07-14.43 p = 0.0038) were independently associated with the degree of ventricular dysfunction in chagasic cardiomyopathy. CCC patients showed greater change in iron metabolism regarding the indeterminate form and other forms of cariomyopathies.


Assuntos
Cardiomiopatia Chagásica/metabolismo , Distúrbios do Metabolismo do Ferro/metabolismo , Ferro/sangue , Disfunção Ventricular Esquerda/metabolismo , Adulto , Anemia/metabolismo , Anemia/fisiopatologia , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Feminino , Humanos , Distúrbios do Metabolismo do Ferro/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estatísticas não Paramétricas , Disfunção Ventricular Esquerda/fisiopatologia
15.
J Am Soc Echocardiogr ; 32(2): 286-295.e3, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30420161

RESUMO

BACKGROUND: Serial echocardiographic studies in chronic Chagas cardiomyopathy are scarce. The aims of this study were to evaluate whether therapy with benznidazole modifies the progression of cardiac impairment and to identify baseline echocardiographic parameters related to prognosis. METHODS: A prospective substudy was conducted in 1,508 patients with chronic Chagas cardiomyopathy randomized to benznidazole or placebo, who underwent two-dimensional echocardiography at enrollment, 2 years, and final follow-up (5.4 years). Left ventricular (LV) ejection fraction, LV wall motion score index (WMSI), indexed left atrial volume, and chamber dimensions were collected and correlated to all-cause death and a composite hard outcome using univariate and multivariate analyses. RESULTS: At enrollment, most patients had normal chamber dimensions, and 70.5% had preserved LV ejection fractions. During follow-up, all chamber dimensions increased similarly in both treatment arms. LV ejection fraction was comparably reduced (55.7 ± 12.7% to 52.1 ± 14.6% vs 56.3 ± 12.7% to 52.8 ± 14.1%) and LV WMSI similarly increased (1.31 ± 0.41 to 1.49 ± 0.03 and 1.27 ± 0.38 to 1.51 ± 0.03) for the benznidazole and placebo groups, respectively (P > .05). A higher baseline LV WMSI was identified in subjects who died compared with those alive at final echocardiography (1.76 ± 0.517 vs 1.271 ± 0.393, P < .0001). There was a significant (P < .0001) graded increase in the risk for the composite outcome with worsening LV WMSI (hazard ratios, 2.27 [95% CI, 1.69-3.06] and 6.42 [95% CI, 4.94-8.33]) and also of death (hazard ratios, 2.45 [95% CI, 1.62-3.71] and 8.99 [95% CI, 6.3-12.82]) for 1 < LV WMSI < 1.5 and LV WMSI > 1.5, respectively. Both LV WMSI and indexed left atrial volume remained independent predictors in multivariate analysis. CONCLUSIONS: Trypanocidal treatment had no effect on echocardiographic progression of chronic Chagas cardiomyopathy over 5.4 years. Despite normal global LV systolic function, regional wall motion abnormalities and indexed left atrial volume identified patients at higher risk for hard adverse clinical outcomes.


Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Ecocardiografia/métodos , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Nitrorredutases/uso terapêutico , Função Ventricular Esquerda/fisiologia , Adolescente , Adulto , Idoso , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Feminino , Seguimentos , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Sístole , Fatores de Tempo , Tripanossomicidas/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
16.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
17.
Microbes Infect ; 21(1): 63-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30071300

RESUMO

Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy. However, the effect of HFD on the subsequent stages of infection - the indeterminate and chronic stages - has not been investigated. To address this gap in knowledge, we studied the effect of HFD during indeterminate and chronic stages of Chagas disease in the mouse model. We report, for the first time, the effect of HFD on myocardial inflammation, vasculopathy, and other types of dysfunction observed during chronic T. cruzi infection. Our results show that HFD perturbs lipid metabolism and induces oxidative stress to exacerbate late chronic Chagas disease cardiac pathology.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Animais , Cardiomiopatia Chagásica/etiologia , Cardiomiopatia Chagásica/metabolismo , Cardiomiopatia Chagásica/patologia , Colesterol/metabolismo , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Mitocôndrias Cardíacas/fisiologia , Estresse Oxidativo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Trypanosoma cruzi/fisiologia
18.
J Electrocardiol ; 51(6): 1039-1043, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497727

RESUMO

Chagas cardiomyopathy is the most harmful complication of Chagas disease. The electrocardiogram is a well-studied exam and has been considered an important tool for detection and evaluation of Chagas cardiomyopathy since the first years of its description. Many of its abnormalities have been described as associated with a worse prognosis. Serum BNP levels were described as inversely related to the left ventricular ejection fraction and as an independent predictor of death. It was not reported how electrocardiographic alterations correlate to NT-proBNP and its analog. The present study aims to describe the baseline electrocardiograms of a large cohort of patients with Chagas disease from endemic area and to establish an association between the number of electrocardiogram alterations and high levels of NT-ProBNP in Chagas disease patients. This study selected 1959 Chagas disease patients in 21 municipalities within a limited region in the northern part of the State of Minas Gerais (Brazil), 1084 of them had Chagas cardiomyopathy. NT-proBNP levels were suggestive of heart failure in 11.7% of this population. One or more electrocardiographic alterations have an Odds Ratio of 9.12 (CI 95% 5.62-14.80) to have NT-proBNP elevation. Considering the association between the number of 1, 2, and 3 or more alterations in electrocardiogram and NT-proBNP elevation, the ORs were 7.11 (CI 95% 4.33-11.67); 16.04 (CI 95% 9.27-27.77) and 47.82 (CI 95% 17.98-127.20), respectively. The presence and the number of typical electrocardiographic alterations of Chagas disease are independently associated with the severity of the cardiomyopathy.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Eletrocardiografia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Biomarcadores/sangue , Brasil , Cardiomiopatia Chagásica/sangue , Doença de Chagas/epidemiologia , Estudos de Coortes , Estudos Transversais , Doenças Endêmicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
19.
Rev Soc Bras Med Trop ; 51(6): 827-830, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30517538

RESUMO

INTRODUCTION: We investigated the occurrence of coronary sinus abnormalities in the indeterminate form of Chagas disease (CD). METHODS: Differences between the maximum and minimum diameters of the coronary sinus (∆%) on echocardiography were evaluated in individuals with the indeterminate form of CD (n=14) and those without (n=16) CD. The association of the difference with abnormalities detected by echocardiography and myocardial scintigraphy was assessed. RESULTS: The mean Δ% values did not differ significantly between the groups. There was no correlation of the measurements with echocardiographic and myocardial scintigraphy findings. CONCLUSIONS: The coronary sinus evaluation revealed no differences between the groups.


Assuntos
Cardiomiopatia Chagásica/diagnóstico por imagem , Seio Coronário/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Cardiomiopatia Chagásica/fisiopatologia , Seio Coronário/parasitologia , Seio Coronário/fisiopatologia , Ecocardiografia , Feminino , Humanos , Masculino , Disfunção Ventricular Esquerda/fisiopatologia
20.
Trials ; 19(1): 507, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30231899

RESUMO

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.


Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Suplementos Nutricionais , Selenito de Sódio/uso terapêutico , Adolescente , Adulto , Idoso , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Suplementos Nutricionais/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Selenito de Sódio/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
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