RESUMO
OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.
Assuntos
Cardiomiopatia Chagásica , Músculos Respiratórios , Humanos , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Músculos Respiratórios/fisiopatologia , Cardiomiopatia Chagásica/fisiopatologia , Adulto , Doença Crônica , Insuficiência Cardíaca/fisiopatologia , Força Muscular/fisiologia , Inalação/fisiologia , Debilidade Muscular/fisiopatologia , Resistência Física , IdosoRESUMO
Sustained interaction between the cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), has been linked to cardiovascular disorders. Chagas cardiomyopathy, elicited by Trypanosoma cruzi infection, is associated with chronic inflammation, fibrosis and hypertrophy. This study aimed to explore the involvement of the TWEAK/Fn 14 axis in development of Chagas heart disease. Parasite infection in vitro triggered Fn14 overexpression in atrial HL-1 myocytes and cardiac MCF fibroblasts. Fn14 levels were also increased in heart tissue from C57BL/6 mice at 130 days post-infection, particularly in myocytes and fibroblasts. Concurrently, TWEAK expression in circulating monocytes from this group was higher than that determined in uninfected controls. TWEAK/Fn14 interaction was functional in myocytes and fibroblasts isolated from infected hearts, leading to TNF receptor-associated factor 2 (TRAF2)-mediated activation of nuclear factor kappa B (NFκB) signaling. Ex vivo stimulation of both cell types with recombinant TWEAK for 24 h boosted the NFκB-regulated production of proinflammatory/profibrotic mediators (IL-1ß, IL-6, TNF-α, IL-8, CCL2, CCL5, MMP-2, MMP-9, ICAM-1, E-selectin) involved in chronic T. cruzi cardiomyopathy. We further evaluated the therapeutic potential of the soluble decoy receptor Fn14-Fc to interfere with TWEAK/Fn14-dependent pathogenic activity. Fn14-Fc treatment of chronically infected mice was effective in neutralizing the ligand and reverting electrocardiographic abnormalities, maladaptive inflammation, adverse remodeling and hypertrophy in myocardium. Altogether, these findings suggest that sustained TWEAK/Fn14 induction by persistent T. cruzi infection is implicated in cardiopathogenesis and make TWEAK/Fn14 axis a promising target for the treatment of chronic Chagas heart disease.
Assuntos
Doença de Chagas , Cardiopatias , Camundongos , Animais , Miócitos Cardíacos , Receptor de TWEAK/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Inflamação , Fibroblastos , Cardiopatias/metabolismo , Hipertrofia/metabolismoRESUMO
BACKGROUND: Chagas heart disease (CHD) impairs the systemic microvascular function. We investigated the effects of exercise training on cutaneous microvascular function among patients with CHD. METHODS: Patients from the PEACH study were randomly assigned to a supervised exercise training 3 times/week for 6 months (Trained; n = 10) or a control group (Untrained; n = 8). Both groups underwent evaluation of microvascular function before, and at 3- and 6-months of follow-up. Cutaneous vascular conductance (CVC) was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh), sodium nitroprusside (SNP) and during post-occlusive reactive hyperemia (PORH). RESULTS: At 3-months of follow-up, no difference was detected between groups in CVC responses to ACh (p = 0.50), SNP (p = 0.26) and HRPO (p = 0.65). However, at 6-months of follow-up, trained vs. untrained patients improved CVC induced by SNP-iontophoresis (0.19 ± 0.10 vs. 0.14 ± 0.15 APU.mmHg-1; p = 0.05) and PORH (0.63 ± 0.15 vs. 0.48 ± 0.18 APU.mmHg-1; p = 0.05). CVC response to ACh-iontophoresis was similar between groups (0.19 ± 0.11 vs. 0.22 ± 0.17 APU.mmHg-1; p = 0.38). CONCLUSION: Exercise training performed during 6 months improved the cutaneous microvascular function of CHD patients. Further studies evaluating the mechanism involved in this response are warranted.
Assuntos
Reabilitação Cardíaca , Cardiomiopatia Chagásica/reabilitação , Terapia por Exercício , Microcirculação , Pele/irrigação sanguínea , Idoso , Brasil , Cardiomiopatia Chagásica/diagnóstico por imagem , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Fatores de Tempo , Resultado do TratamentoRESUMO
Cardiac damage during the acute phase of Chagas disease (CD) is associated with an increase in pro-inflammatory markers and oxidative stress. Melatonin (MEL) has emerged as a promising therapy for CD due to its antioxidant and immunomodulatory properties; however, the protective action of MEL in the cardiac tissue, as well as its direct action on the parasite cycle, is not fully understood. We investigated the effects of MEL on heart parasitism in mice infected with Trypanosoma cruzi and also its effects on the parasitic proliferation in vitro. Our in vivo study showed that MEL reduced circulating parasitemia load, but did not control tissue (heart, liver, and spleen) parasitism in mice. MEL did not prevent the redox imbalance in the left ventricle of infected mice. Our in vitro findings showed that MEL did not inhibit parasites replication within cells, but rather increased their release from cells. MEL did not control parasitism load in the heart or prevent the cardiac redox imbalance induced by acute T. cruzi infection. The hormone controlled the circulating parasitic load, but within cells MEL accelerated parasitic release, a response that can be harmful.
Assuntos
Melatonina , Trypanosoma cruzi , Animais , Doença de Chagas , Coração , CamundongosRESUMO
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease. This neglected tropical disease causes severe morbidity and mortality in endemic regions. About 30% of T. cruzi infected individuals will present with cardiac complications. Invasive trypomastigotes released from infected cells can be carried in the vascular endothelial system to infect neighboring and distant cells. During the process of cellular infection, the parasite induces host cells, to increase the levels of host thrombospondin-1 (TSP-1), to facilitate the process of infection. TSP-1 plays important roles in the functioning of vascular cells, including vascular endothelial cells with important implications in cardiovascular health. Many signal transduction pathways, including the yes-associated protein 1 (YAP)/transcriptional coactivator, with PDZ-binding motif (TAZ) signaling, which are upstream of TSP-1, have been linked to the pathophysiology of heart damage. The molecular mechanisms by which T. cruzi signals, and eventually infects, heart endothelial cells remain unknown. To evaluate the importance of TSP-1 expression in heart endothelial cells during the process of T. cruzi infection, we exposed heart endothelial cells prepared from Wild Type and TSP-1 Knockout mouse to invasive T. cruzi trypomastigotes at multiple time points, and evaluated changes in the hippo signaling cascade using immunoblotting and immunofluorescence assays. We found that the parasite turned off the hippo signaling pathway in TSP-1KO heart endothelial cells. The levels of SAV1 and MOB1A increased to a maximum of 2.70 ± 0.23 and 5.74 ± 1.45-fold at 3 and 6 h, respectively, in TSP-1KO mouse heart endothelial cells (MHEC), compared to WT MHEC, following a parasite challenge. This was accompanied by a significant continuous increase in the nuclear translocation of downstream effector molecule YAP, to a maximum mean nuclear fluorescence intensity of 10.14 ± 0.40 at 6 h, compared to wild type cells. Furthermore, we found that increased nuclear translocated YAP significantly colocalized with the transcription co-activator molecule pan-TEAD, with a maximum Pearson's correlation coefficient of 0.51 ± 0.06 at 6 h, compared to YAP-Pan-TEAD colocalization in the WT MHEC, which decreased significantly, with a minimum Pearson's correlation coefficient of 0.30 ± 0.01 at 6 h. Our data indicate that, during the early phase of infection, upregulated TSP-1 is essential for the regulation of the hippo signaling pathway. These studies advance our understanding of the molecular interactions occurring between heart endothelial cells and T. cruzi, in the presence and absence of TSP-1, providing insights into processes linked to parasite dissemination and pathogenesis.
Assuntos
Transporte Ativo do Núcleo Celular/fisiologia , Células Endoteliais/parasitologia , Mioblastos/parasitologia , Miocárdio/citologia , Proteínas de Protozoários/fisiologia , Trombospondina 1/fisiologia , Trypanosoma cruzi/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células Endoteliais/metabolismo , Técnicas de Inativação de Genes , Camundongos , Mioblastos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Transdução de Sinais/fisiologia , Trombospondina 1/deficiência , Transativadores/fisiologiaRESUMO
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 TratamentoRESUMO
PURPOSE: To verify the prognostic value of health-related quality of life (HRQoL) and the differences in HRQoL and clinical variables between groups of Chagas heart disease (CHD) patients with and without cardiovascular adverse events. METHODS: Seventy-five CHD patients were evaluated by echocardiography, maximal exercise testing, and Short-form of Health Survey (SF-36) Questionnaire. Patients were followed during 6 years. In the statistical analysis, uni- and multivariate Cox regression were performed to verify the accuracy of the HRQoL in predicting cardiovascular events. RESULTS: After the follow-up period (41 ± 12 months), 20 patients (27%) had adverse events. Those with poor outcome had lower left ventricular ejection fraction (LVEF) (p = 0.002), higher left ventricular end-diastolic diameter (LVDd) (p = 0.019), and worse scores in general health perceptions (p = 0.047), social role functioning (p = 0.026), and mental component summary (p = 0.043) of SF-36. Patients with lower LVEF (p = 0.003), higher LVDd (p = 0.022), worse HRQoL in the general heath perceptions domain (p = 0.022), and mental component summary (p = 0.031) were associated with worse prognosis. In the multivariate Cox regression, LVEF (HR 0.94, 95% CI from 0.90 to 0.98, p = 0.007) and mental component summary (HR 0.98, 95% CI from 0.94 to 1.00, p = 0.047) remained as independent predictors of adverse events in CHD patients. CONCLUSION: The assessment of HRQoL, especially the mental component, should be taken into account to provide an accurate prognosis in addition to other well-established predictors of poor outcomes in CHD patients.
Assuntos
Cardiomiopatia Chagásica/psicologia , Cardiopatias/psicologia , Qualidade de Vida/psicologia , Cardiomiopatia Chagásica/patologia , Feminino , Inquéritos Epidemiológicos , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
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-IdadeRESUMO
BACKGROUND: It has been difficult to prove that "catecholamine-induced cardiomyopathy" contributes to the mechanism of sudden cardiac death in Chagas heart disease. Also, it is almost impossible to rule out the possibility that it is not involved in the process. More importantly, the vagal-cholinergic pathway in the ventricle plays a direct role in the prevention of the initiation of complex ventricular arrhythmias, including nonsustained ventricular tachycardia, ventricular fibrillation responsible for sudden death. OBJECTIVE: To determine frequency of parasympathetic autonomic indices among the different groups of risk of cardiovascular death when stratified by Rassi score. METHODS: Patients with Chagas heart disease were selected and divided into three risk groups by Rassi score. A fourth group, non-Chagas group, was of similar age and gender. All were subjected to analysis of heart rate variability during controlled breathing (RSA) and tilt table passive test (tilt test). High frequency and low frequency/high frequency ratio were calculated and presented by box-plot. Also, t-test was used to compare the two groups. RESULTS: It was observed that the parasympathetic and sympathetic component were affected, when the risk group increased the response was worsened to the stimulus (RSA or Tilt). Also, the low-risk group was jeopardized, when compared to the non-Chagas group. CONCLUSION: The loss of parasympathetic modulation was present in all Rassi risk groups, including the low risk, indicating that a morphological change of the myocardium represents a detectable neurofunctional change.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Chagásica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cardiomiopatia Chagásica/mortalidade , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Teste da Mesa InclinadaRESUMO
The aim of this study was to investigate the plasma levels of the CCL3 and CCL4 chemokines in patients with the cardiac and digestive clinical forms of chronic Chagas disease and in cardiac patients with and without left ventricular systolic dysfunction (LVSD). Plasma samples from 75 patients were evaluated by enzyme-linked immunosorbent assay (ELISA) to confirm infection by T. cruzi. Plasma levels of the CCL3 and CCL4 chemokines were measured using Milliplex® MAP assay (Millipore). There were no significant differences in the levels of CCL3 and CCL4 between patients with the digestive and cardiac clinical forms of Chagas disease. Moreover, no significant differences were found between patients without LVSD and those with LVSD. Higher CCL3 and CCL4 plasma levels were found in patients with LVSD compared to those with the digestive form of the disease. The CCL3 and CCL4 chemokines might not be involved in differential susceptibility to the digestive and cardiac clinical forms of chronic Chagas disease, and it seems they do not influence the development of LVSD.
Assuntos
Doença de Chagas/sangue , Quimiocina CCL3/sangue , Quimiocina CCL4/sangue , Gastroenteropatias/sangue , Trypanosoma cruzi , Disfunção Ventricular Esquerda/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Since a male-related higher cardiovascular morbidity and mortality in patients with Chagas' heart disease has been reported, we aimed to investigate gender differences in myocardial damage assessed by cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: Retrospectively, 62 seropositive Chagas' heart disease patients referred to CMR (1.5 T) and with low probability of having significant coronary artery disease were included in this analysis. Amongst both sexes, there was a strong negative correlation between LV ejection fraction and myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males showing significantly greater myocardial fibrosis (P = 0.002) and lower LV ejection fraction (P < 0.001) than females. After adjustment for potential confounders, gender remained associated with myocardial dysfunction, and 53% of the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also, the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P < 0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P = 0.003). CONCLUSIONS: We observed gender-related differences in myocardial damage assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis and myocardial dysfunction are associated to cardiovascular outcomes, our findings might help to understand the poorer prognosis observed in males in Chagas' disease.
Assuntos
Cardiomiopatia Chagásica/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Adulto , Idoso , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/fisiopatologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Feminino , Fibrose , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Volume Sistólico , Função Ventricular Esquerda , Remodelação VentricularRESUMO
MICA-129 polymorphism affects the binding affinity of MICA molecules with the NKG2D receptor and influences effector cell function. The genotype met/met was associated with the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease, while the val/val genotype was associated with the absence of LVSD.
Assuntos
Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/fisiopatologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Polimorfismo Genético , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Alelos , Doença Crônica , Feminino , Genes MHC Classe I , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fatores de Risco , Disfunção Ventricular Esquerda/diagnósticoRESUMO
About 6.5 million people are infected with Chagas disease (CD) globally, and WHO estimates that $ > million people worldwide suffer from ChHD. Sudden cardiac death (SCD) represents one of the leading causes of death worldwide and affects approximately 65% of ChHD patients at a rate of 24 per 1000 patient-years, much greater than the SCD rate in the general population. Its occurrence in the specific context of ChHD needs to be better exploited. This paper provides the first evidence supporting the use of machine learning (ML) methods within non-invasive tests: patients' clinical data and cardiac restitution metrics (CRM) features extracted from ECG-Holter recordings as an adjunct in the SCD risk assessment in ChHD. The feature selection (FS) flows evaluated 5 different groups of attributes formed from patients' clinical and physiological data to identify relevant attributes among 57 features reported by 315 patients at HUCFF-UFRJ. The FS flow with FS techniques (variance, ANOVA, and recursive feature elimination) and Naive Bayes (NB) model achieved the best classification performance with 90.63% recall (sensitivity) and 80.55% AUC. The initial feature set is reduced to a subset of 13 features (4 Classification; 1 Treatment; 1 CRM; and 7 Heart Tests). The proposed method represents an intelligent diagnostic support system that predicts the high risk of SCD in ChHD patients and highlights the clinical and CRM data that most strongly impact the final outcome.
Assuntos
Morte Súbita Cardíaca , Aprendizado de Máquina , Humanos , Teorema de Bayes , Morte Súbita Cardíaca/epidemiologia , Medição de Risco , EletrocardiografiaRESUMO
Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilised electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST, and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodelling and for examining the potential of antiparasitic drugs to prevent or alleviate CCC development and progression.
RESUMO
INTRODUCTION: Myocardial ischemia is common in patients with chronic Chagas cardiomyopathy (CCC), but only recently clinical and experimental studies highlighted the involvement of this abnormality as contributing to the progression of myocardial damage. AREAS COVERED: Despite the absence of obstructive epicardial coronary artery disease at angiography, and limited evidence of abnormal flow regulation at the macrovascular level, remarkable functional and structural microvascular abnormalities are consistently reported by independent investigations of CCC. These derangements occur early and contribute to myocardial dysfunction. Recent research focused on reversing microvascular dysfunction as a target to positively impact the course of CCC. We conducted an extensive review of the scientific literature, aiming to summarize the role of coronary dysfunction causing myocardial ischemia in CCC, with a focus on implications for clinical management of individuals affected by this disease. EXPERT OPINION: Preclinical studies showed a clear correlation between perfusion defects and inflammation in viable but impaired dysfunctional myocardium. These findings provided further insight into the CCC complex pathophysiology and support the role of very few recent therapeutic interventions aiming to relieve myocardial ischemia. Further research is warranted to assess the efficacy of new interventions addressing reversal of microvascular ischemia and inflammation modulation and halting ventricular dysfunction progression in CCC.
Assuntos
Cardiomiopatias , Cardiomiopatia Chagásica , Doença de Chagas , Doença da Artéria Coronariana , Isquemia Miocárdica , Humanos , Isquemia Miocárdica/etiologia , Doença de Chagas/complicações , Inflamação , Vasos CoronáriosRESUMO
Background: In the USA, â¼300 000 people are affected by Chagas heart disease, a growing, but commonly overlooked, public health issue. Chagas as a potential aetiology of dilated cardiomyopathy remains under-recognized. We present a case where multimodality imaging was essential in the diagnosis and management of Chagas heart disease. Case summary: A 54-year-old man, originally from Mexico, presented to the emergency department with chest pain and recurrent syncopal episodes, found to be in haemodynamically unstable ventricular tachycardia (VT) requiring urgent cardioversion. Urgent coronary angiography revealed no obstructive disease. A transthoracic echocardiogram revealed moderately reduced left ventricular systolic function (left ventricular ejection fraction 35-40%) with apical akinesis and an aneurysm of the apical septum. Cardiac magnetic resonance (CMR) confirmed a prominent apical aneurysm with dyskinesis of the apical septum, with the evidence of transmural myocardial late gadolinium enhancement of the entire left ventricular apex and a small apical thrombus. Serologic testing was positive for Trypanosoma cruzi IgG antibody, which was confirmed on repeat testing at the Centers for Disease Control and Prevention. Patient underwent VT ablation and was discharged on guideline-directed medical therapy including a regimen of anticoagulation, beta-blocker, and angiotensin-converting enzyme inhibitor therapies. He has had no subsequent syncope or VT. Discussion: Chagas heart disease remains under-recognized and under-diagnosed despite the growing burden of T. cruzi infection in the USA. Suspicion for Chagas heart disease should be considered in patients presenting with heart failure symptoms and ventricular arrhythmias with the right corresponding history and imaging findings on echocardiogram and CMR.
RESUMO
Coronavirus disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; CoV2) is a deadly contagious infectious disease. For those who survive COVID-19, post-COVID cardiac damage greatly increases the risk of cardiomyopathy and heart failure. Currently, the number of COVID-related cases are increasing in Latin America, where a major COVID comorbidity is Chagas' heart disease, which is caused by the parasite Trypanosoma cruzi. However, the interplay between indeterminate Chagas disease and COVID-19 is unknown. We investigated the effect of CoV2 infection on heart pathology in T. cruzi infected mice (coinfected with CoV2 during the indeterminate stage of T. cruzi infection). We used transgenic human angiotensin-converting enzyme 2 (huACE2/hACE2) mice infected with CoV2, T. cruzi, or coinfected with both in this study. We found that the viral load in the hearts of coinfected mice is lower compared to the hearts of mice infected with CoV2 alone. We demonstrated that CoV2 infection significantly alters cardiac immune and energy signaling via adiponectin (C-ApN) and AMP-activated protein kinase (AMPK) signaling. Our studies also showed that increased ß-adrenergic receptor (b-AR) and peroxisome proliferator-activated receptors (PPARs) play a major role in shifting the energy balance in the hearts of coinfected female mice from glycolysis to mitochondrial ß-oxidation. Our findings suggest that cardiac metabolic signaling may differently regulate the pathogenesis of Chagas cardiomyopathy (CCM) in coinfected mice. We conclude that the C-ApN/AMPK and b-AR/PPAR downstream signaling may play major roles in determining the progression, severity, and phenotype of CCM and heart failure in the context of COVID.
RESUMO
BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, has been increasingly encountered as a cause of cardiovascular disease in the United States. We aimed to examine trends of hospital admissions and cardiovascular outcomes of cardiac CD (CCD). METHODS: Search of 2003-2011 Nationwide Inpatient Sample database identified 949 (age 57±16 years, 51% male, 72.5% Hispanic) admissions for CCD. RESULTS: A significant increase in the number of admissions for CCD was noted during the study period (OR=1.054; 95% CI=1.028-1.081; P< 0.0001); 72% were admitted to Southern and Western hospitals. Comorbidities included hypertension (40%), coronary artery disease (28%), hyperlipidemia (26%), tobacco use (12%), diabetes (9%), heart failure (5%) and obesity (2.2%). Cardiac abnormalities noted during hospitalization included atrial fibrillation (27%), ventricular tachycardia (23%), sinoatrial node dysfunction (5%), complete heart block (4%), valvular heart disease (6%)] and left ventricular aneurysms (5%). In-hospital mortality was 3.2%. Other major adverse events included cardiogenic shock in 54 (5.7%), cardiac arrest in 30 (3.2%), acute heart failure in 88 (9.3%), use of mechanical circulatory support in 29 (3.1%), and acute stroke in 34 (3.5%). Overall, 63% suffered at least one adverse event. Temporary (2%) and permanent (3.5%) pacemakers, implantable cardioverter defibrillators (10%), and cardiac transplant (2.1%) were needed for in-hospital management. CONCLUSIONS: Despite the remaining concerns about lack of awareness of CCD in the US, an increasing number of hospital admissions were reported from 2003-2011. Serious cardiovascular abnormalities were highly prevalent in these patients and were frequently associated with fatal and nonfatal complications.
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 , Imageamento 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/fisiopatologiaRESUMO
OBJECTIVES: The goal of this analysis was to pool data from published studies on outcomes after implantable cardioverter-defibrillator (ICD) therapy in patients with Chagas heart disease (CHD). BACKGROUND: CHD is characterized by a high burden of ventricular arrhythmias and an increased risk of sudden cardiac death. The indications for ICD are not well established. METHODS: An extensive literature search without language restrictions was performed to identify all studies on ICD therapy in patients with CHD. A random effects model was used to calculate percentages and 95% confidence intervals (CIs). RESULTS: Of 397 articles screened, 13 studies (all observational) were included. There were 1,041 patients (mean age at implantation 57 ± 11 years; 64% men), most of whom (92%) received an ICD for secondary prevention. Antiarrhythmic medication consisted of amiodarone (79%) and beta-blockers (44%). Overall, the annual all-cause mortality rate was 9.0% (95% CI: 6.9 to 11.7) in 2.8 ± 1.9 years of follow-up, and the annual sudden cardiac death rate was 2.0% (95% CI: 1.3 to 3.3) in 2.6 ± 1.9 years. In addition, 24.8% (95% CI: 15.7 to 37.0) of patients received 1 or more appropriate interventions (shocks or antitachycardia pacing), 4.7% (95% CI: 3.2 to 6.9) received inappropriate shocks, and 9.1% (95% CI: 5.5 to 14.7) had electric storms annually. CONCLUSIONS: In patients with an ICD, annual all-cause mortality rate was 9%. Appropriate ICD interventions and electric storms were frequent, occurring at a rate of 25% and 9% per year, respectively. Inappropriate ICD shocks were not infrequent (5% per year). The benefits and risks of ICD therapy in patients with CHD should be carefully weighed until data from better studies become available.