Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is ...associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.
Abstract Background Angiotensin-converting enzyme (ACE) 2 is a novel homologue of ACE. It metabolizes angiotensin (Ang)II to Ang-(1-7). This study aims to investigate the diagnostic and prognostic ...potency of circulating ACE2 activity in patients with heart failure (HF) from Chagas' disease (CD). Methods and Results Blood samples were obtained from 111 CD patients and 40 age- and gender-matched healthy subjects. The CD patients were further subdivided according to their New York Heart Association classification. ACE2 activity was significantly increased in CD patients with HF, but not in patients without systolic dysfunction. Moreover, plasma ACE2 activity was significantly correlated with their clinical severity and echocardiographic parameters. Importantly, the potency of circulating ACE2 activity in CD patients was equally potent as that of B-type natriuretic peptide to predict cardiac death and heart transplant. Most importantly, patients with both parameters elevated were on a 5-fold higher risk to reach an endpoint than patients with increase in only 1 of the 2 parameters. Conclusions Determination of ACE2 activity may provide a new and important diagnostic and prognostic marker for patients with CD. ACE2 activity and BNP concentration have additive predictive value and may be used in combination to offer a new dimension of prediction in HF.
Brazilian Society of Cardiology - The Women's Letter Oliveira, Glaucia Maria Moraes de; Negri, Fátima Elizabeth Fonseca de Oliveira; Clausell, Nadine Oliveira ...
Arquivos brasileiros de cardiologia,
06/2019, Letnik:
112, Številka:
6
Journal Article
Chagas disease (CD), which is caused by the protozoan Trypanosoma cruzi, is a major cause of heart failure in Latin America. We investigated if plasma activity of one of the enzymes being part of the ...renin–angiotensin system, aminopeptidase A (APA), has diagnostic and prognostic potency in patients with CD and dilated cardiomyopathies (DCMs) due to other causes. Blood samples were taken from 94 patients with CD, 46 patients with DCM, and 34 healthy control subjects. Plasma APA activity was determined by fluorometry assays. The average follow-up time was 39 months; by the end of study, 33 patients had died and another 13 received heart transplant. There was no significant alteration in plasma APA activity in the patients with CD or DCM, as compared with that in controls. The Pearson correlation of echocardiographic data with plasma APA activity in patients with CD and DCM did not reveal any significant correlation with left-ventricular ejection fraction or other echocardiographic parameters. APA activity was unable to predict mortality or the need for heart transplant. Detection of APA activity in plasma may not prove suitable for prognosis in patients with heart failure and is unable to screen or diagnose asymptomatic patients with CD for early therapy.
We have previously shown that a low-stringency single-specific primer-polymerase chain reaction (LSSP- PCR) is a highly sensitive and reproducible technique for the genetic profiling of Trypanosoma ...cruzi parasites directly in tissues from infected animals and humans. By applying LSSP-PCR to the study of the variable region of kinetoplast minicircle from T. cruzi, the intraspecific polymorphism of the kinetoplast-deoxyribonucleic acid (kDNA) sequence can be translated into individual kDNA signatures. In the present article, we report on our success using the LSSP-PCR technique in profiling the T. cruzi parasites present in the hearts of 13 patients with chagasic cardiopathy and in the esophagi of four patients (three of them with chagasic megaesophagus). In two patients, one with the cardiodigestive clinical form of Chagas disease and the other with cardiopathy and an esophageal inflammatory process, we could study both heart and esophagus and we detected distinct kDNA signatures in the two organs. This provides evidence of a differential tissue distribution of genetically diverse T. cruzi populations in chronic Chagas disease, suggesting that the genetic variability of the parasite is one of the determining factors of the clinical form of the disease.
Atrial and B-type natriuretic peptides (ANP and BNP), but not C-type natriuretic peptide (CNP), have been identified to be diagnostic and prognostic markers in Chagas disease (CD). Although ANP and ...BNP excessively rise in patients with CD, increase in CNP is just minor. Our study aimed to investigate the mechanisms leading to CNP insensitivity to heart failure (HF) stimuli. Amino-terminal fragment of CNP precursor (NT-proCNP) and activity of neutral endopeptidase (NEP) were quantified to monitor CNP generation and degradation, respectively. Blood samples were collected from patients with CD and control healthy subjects. NT-proCNP concentrations were significantly lower in patients with CD without systolic dysfunction compared with healthy subjects. Despite a trend toward increase with rising heart failure clinical severity, it was significantly correlated with left ventricular ejection fraction and other echocardiographic parameters. As shown for CNP before, NT-proCNP could not predict mortality and heart transplant. Importantly, it had no statistical correlation with CNP. Additionally, NEP activity was significantly increased in New York Heart Association III and IV patients with HF but was positively correlated with CNP concentration. Our data demonstrates that generation of CNP is not enhanced under HF condition like CD. Thus, CNP rise by severe HF is caused by its less degradation that is independent of NEP acitivity.
► Stem cell growth factor (SCGF) beta was significantly increased in advanced heart failure patients. ► Its concentration has no correlation with echocardiographic parameters in these patients. ► Its ...prognostic value for death and heart transplantation for heart failure patients is poor.
Chagas’ disease (CD) often leads to dilated cardiomyopathy (DCM), and during its chronic stage hematopoietic stem or progenitor cells are involved in its pathological process. However, it is not clear whether stem cell growth factor (SCGF) beta can be regulated in patients with CD and idiopathic DCM. In present study, we aim to investigate the plasma SCGF beta concentration and its correlation with echocardiographic parameters and clinical outcome.
In this prospective cohort study, SCGF beta levels were quantified in patients with CD (n=94), DCM (n=48), and control healthy subjects (n=25). In comparison with healthy subjects, no statistical difference can be detected in NYHA classes I–II patients. However, SCGF beta was significantly increased in advanced heart failure patients (NYHA III–IV), compared to CD patients without heart failure. There was no group difference between CD and DCM. However, despite this significant increase in advanced heart failure patients, SCGF beta had no significant correlation with echocardiographic parameters, and it cannot be used as a prognostic marker for mortality and heart transplantation.
To our best knowledge, this is the first report of SCGF beta in heart failure patients. Although it is significantly increased in advanced heart failure patients caused by CD or DCM, its prognostic value for end points is minor.
To determine the diagnostic and prognostic value of natriuretic peptides in patients with Chagas’ disease (CD), the authors first measured atrial (ANP), B‐type (BNP), and C‐type natriuretic peptide ...(CNP) and compared their diagnostic and prognostic capacity with that in other dilated cardiomyopathies (DCM). The CD and DCM patients were subdivided according to their New York Heart Association (NYHA) classification. Circulating ANP and more pronounced BNP, but not CNP, were increased in CD and DCM patients in relation to NYHA class. Importantly, ANP and BNP were already significantly elevated in CD patients without systolic ventricular dysfunction. All 3 natriuretic peptides were correlated with echocardiographic parameters in CD patients. While ANP and BNP have high predictive value for mortality and necessity for heart transplant in CD, CNP can not predict them. Thus, ANP and BNP rather than CNP could be used as valuable molecular markers to identify asymptomatic CD patients for early therapy and predict clinical outcomes.
Plasma angiotensin-converting enzyme (ACE) 2 activity has been demonstrated to be an independent prognostic marker in Chagasʼ disease, equally potent as B-type natriuretic peptide. This study aimed ...to investigate the prognostic potency of circulating ACE2 activity in patients with idiopathic dilated cardiomyopathy (DCM). Blood samples were withdrawn from patients with idiopathic DCM and healthy control subjects. The DCM patients were subdivided into 2 groups according to their New York Heart Association classification. The plasma ACE2 activity was measured by a fluorescence method. Plasma ACE2 activity was significantly increased in DCM patients, correlating with clinical severity. It was correlating with echocardiographic parameters in patients with DCM. Furthermore, plasma ACE2 activity had the potency to predict cardiac death and heart transplantation. However, compared with patients with Chagasʼ disease, the correlation and predictive value of ACE2 activity in patients with DCM was much less pronounced. Beta blocker treatment in patients with DCM was identified to prevent the association between circulating ACE2 activity and echocardiographic parameters. Although ACE2 activity in blood samples of patients with DCM without beta blockers is potent in correlating with the severity of disease and in predicting death and heart transplantation, its correlation and prediction potency are significantly diminished by beta blocker treatment.
Atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP) are powerful neurohormonal indicators of left-ventricular function and prognosis in heart failure (HF). Chagas disease (CD) ...caused by the protozoan Trypanosoma cruzi remains a major cause of HF in Latin America. We assessed whether the plasma concentration of the third natriuretic peptide, C-type natriuretic peptide (CNP), also has diagnostic and prognostic properties in patients with CD or other dilated cardiomyopathies (DCM).Blood samples were obtained from 66 patients with CD, 50 patients with DCM from other causes, and 30 gender- and age-matched healthy subjects. Patients were subdivided according to the New York Heart Association (NYHA) class. The CNP concentration was determined by radioimmunoassay (Immundiagnostik, Bensheim, Germany).The main duration of follow-up was 31.4 months (range 13 to 54 months); 19 patients had died and 11 patients received a heart transplant. CNP concentrations were only significantly altered in patients with DCM or CD of the NYHA classes III and IV (P < 0.05). The Pearson correlation of echocardiographic data with CNP revealed an association only with the left-ventricular end systolic volume (P = 0.03) in patients with DCM. Furthermore, CNP did not predict mortality or the necessity for heart transplant.Our data are the first to demonstrate the raised levels of the third natriuretic peptide CNP in CD and other DCM. Whereas ANP and BNP have a high predictive value for mortality in both diseases, CNP is without any predictive potency.
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