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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 [+ or -] 3.3 [micro]U/mL) when compared with control (8.0 [+ or -] 4.9 [micro]U/mL) and IDC (9.9 [+ or -] 5.0 [micro]U/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 [micro]g/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.Key words: adipocytokine, insulin levels, Chagas heart disease.Les systemes metabolique, inflammatoire et nerveux autonome presentent des dysfonctionnements chez les patients atteints d'insuffisance cardiaque. Cependant, on ne sait pas si l'etiologie de ces modifications est liee au dysfonctionnement du ventricule gauche ou a l'insuffisance cardiaque. Nous avons evalue le metabolisme et l'activite inflammatoire chez des patients atteints de cardiomyopathie dilatee idiopathique (CDI) ou de cardiomyopathie de Chagas (CCH), ainsi que leur correlation avec le systeme nerveux autonome (SNA). Nous avons reparti 46 patients dans 3 groupes : CDI, CCH et temoin (GT). Nous avons evalue les taux d'adiponectine, de leptine, d'insuline, d'interleukine 6 et du facteur de necrose tumorale alpha. Le SNA a ete evalue par la variabilite de la frequence cardiaque dans le temps et les domaines de frequence a l'aide d'une surveillance de 24 heures par Holter. Les taux de glucose, de cholesterol, de leptine et d'adiponectine ne se sont pas reveles differents entre les groupes. Les taux d'insuline etaient moins eleves dans le groupe CCH (5,4 [+ or -] 3,3 [micro]U/mL) que dans les groupes GT (8,0 [+ or -] 4,9 [micro]U/mL) et CDI (9,9 [+ or -] 5,0 [micro]U/mL) (p = 0,007). Dans le groupe CCH, les taux d'insuline etaient directement proportionnels au ratio LFr/HFr (basses frequences sur hautes frequences; r = 0,562; p = 0,029) et a la composante LFr (r = 0,562; p = 0,029), ainsi qu'inversement proportionnels aux taux d'adiponectine (r = -0,603; p = 0,017). L'ajout d'une unite d'adiponectine entrainait une diminution des taux d'insuline moyens de 0,332 [micro]g/mL. Les taux d'insuline etaient plus bas dans le groupe CCH que dans le groupe CDI et associes aux indices du SNA et aux taux d'adiponectine. [Traduit par la Redaction]Mots-cles : adipocytokine, taux d'insuline, maladie cardiaque de Chagas., IntroductionChagas disease occurs from the southern United States to Patagonia and affects around 8 million people in Latin America and is the main cause of cardiomyopathy in these endemic areas [...]

Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central and South America. Thirty percent of cases evolve into chronic chagas cardiomyopathy (CCC), which has worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that the mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate, and severe CCC patients. An MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with healthy Brazilian individuals. The European lineage is associated with protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. Using mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of chronic chagas disease cardiomyopathy. [ABSTRACT FROM AUTHOR]

Myocardial remodeling includes inappropriate collagen deposition in the interstitium. Erythropoietin (EPO) may have cardioprotective effects. We aimed to assess the role of EPO on myocardial remodeling during the chronic phase. We studied 60 Wistar rats divided into the following groups: control (CT), control + EPO (CT + EPO), myocardial infarction + EPO (MI + EPO), and myocardial infarction (MI). The interstitial collagen volume fraction (ICVF) was quantified and echocardiography was performed. We quantified asymmetric dimethylarginine and glutathione by ELISA, and used real-time PCR to assess apoptosis and inflammation. Western blotting was used to evaluate inflammatory proteins and tissue inhibitors of metalloproteinases (TIMPs), and TUNEL staining was used to detect apoptosis. For matrix metalloproteinases (MMPs), we performed zymography. Parametric and nonparametric analyses were performed according to normality testing. ICVF was greater in MI groups (p < 0.001) and was attenuated by EPO (p = 0.05). The MMP-2 did not show any difference between groups. The TIMP-1 and TIMP-2 did not have difference between groups. The MI groups had worse fraction shortening (p < 0.001), without EPO protection (p = 0.666). The MI groups had increased left ventricle diastolic dimension (p < 0.001) without EPO attenuation (p = 0.79). EPO did not act on oxidative stress. Apoptosis and inflammation were not modulated by EPO. We concluded that EPO attenuated interstitial collagen accumulation, but did not protect from heart dilation or dysfunction. Key words: erythropoietin, ventricular remodeling, fibrosis, myocardial infarction, inflammation, oxidative stress. Resume : Le remodelage du myocarde comprend le depot inapproprie de collagene dans le tissu interstitiel. Par ailleurs, l'erythropoietine (EPO) pourrait avoir des effets cardioprotecteurs. Nous visions a evaluer le role de l'EPO sur le remodelage du myocarde pendant la phase chronique. Nous avons etudie 60 rats Wistar repartis dans les groupes suivants: temoin (T), temoin + EPO (T + EPO), infarctus du myocarde + EPO (IM + EPO) et infarctus du myocarde (IM). Nous avons quantifie la fraction volumique du collagene interstitiel (FVCI) et effectue une echocardiographie. En vue d'evaluer l'apoptose et l'inflammation, nous avons quantifie les taux de dymethylarginine asymetrique et de glutathion a l'aide des techniques d'ELISA et de PCR en temps reel. Nous avons utilise l'immunobuvardage de Western pour evaluer les taux de proteines inflammatoires et d'inhibiteurs des metalloproteinases tissulaires (TIMP), ainsi que la technique de marquage TUNEL pour deceler l'apoptose. Pour les metalloproteinases matricielles (MMP), nous avons effectue une zymographie. Nous avons enfin effectue des analyses parametriques et non parametriques en fonction de tests de distribution normale. La FVCI etait plus elevee dans les groupes IM (p < 0,001) et diminuait avec l'EPO (p = 0,05). Les taux de MMP-2 ne se sont pas reveles differents entre les groupes. L'activite de TIMP-1 et de TIMP-2 n'etait pas differente entre les groupes non plus. En fait, la fraction de raccourcissement etait moins avantageuse dans les groupes IM (p < 0,001), sans protection liee a l'EPO (p = 0,666). Et la dimension du ventricule gauche en diastole etait plus elevee dans les groupes IM (p < 0,001), sans attenuation liee a l'EPO non plus (p = 0,79). Enfin, l'EPO n'avait aucun effet sur le stress oxydatif et elle ne participait pas a la modulation de l'apoptose ni de l'inflammation. Nous en sommes arrives a la conclusion que l'EPO permettait de diminuer l'accumulation de collagene dans le tissu interstitiel, mais qu'elle n'entramait pas de protection contre la dilatation du creur ni contre son dysfonctionnement. [Traduit par la Redaction] Mots-cles: erythropoietine, remodelage des ventricules, fibrose, infarctus du myocarde, inflammation, stress oxydatif., Introduction Myocardial remodeling is responsible for cardiac dysfunction that results in heart failure. Interstitial collagen deposition into the myocardium has a pivotal role in this scenario. Inflammation, oxidative stress, and [...]

OBJECTIVE: To evaluate the clinical meaning of ascites and the main features of patients with ascites and endomyocardial fibrosis. METHODS: We studied 166 patients with endomyocardial fibrosis (mean age 37 years, 114 women) treated over the last 20 years. Ventriculography findings, surgery or necropsy confirmed the diagnosis in all patients. Most patients belonged to New York Heart Association Functional Class III/IV (134, 83.7%). Eighty-one (50.6%) had biventricular, 28 (17.5%) had right ventricular, and 51 (31.8%) had left ventricular involvement. During follow-up, 56 patients died. RESULTS: Ascites was present in 67 (41.8%) patients, and right ventricular involvement was present in 59 (88%). In the comparison between patients with or without ascites, those with ascites had higher mortality (49.2% and 24.7%, respectively). Patients with ascites had a higher incidence of edema (95% vs. 43%), hepatomegaly (5.8cm vs. 4.1cm), mean right atrium pressure (19.3 vs. 12mmHg), and final right ventricle diastolic pressure (18.7 vs. 12.9mmHg). Also, patients with ascites had a longer history of illness (5.1 and 3.9 years, respectively) and had atrial fibrillation more frequently (44.7% vs. 30.1%). CONCLUSION: Ascites was observed in less than 50% of cases of endomyocardial fibrosis and was associated with greater involvement of the right ventricle and with a longer duration of the disease, thus being a characteristic of a worse prognosis.

Chagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) ≥ 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology. [ABSTRACT FROM AUTHOR]

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the oftenfatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease. [ABSTRACT FROM AUTHOR]

Após 1989, introduzimos algumas alterações no tratamento cirúrgico dos aneurismas e dissecções da aorta, em nosso Serviço, entre elas maior rapidez no diagnóstico, uso de parada circulatória, hipotermia profunda, parada circulatória total, monitorização hemodinâmica, controle dos distúrbios de coagulação, controle da pressão liquórica, implantação das artérias intercostais. Entre janeiro de 1980 e julho de 1994, 520 pacientes foram submetidos a tratamento cirúrgico de aneurismas ou dissecções da aorta, de forma consecutiva e não selecionados. Os pacientes foram divididos em três grupos, de acordo com o diagnóstico: ? Aneurisma de aorta ascendente (AAAS) ? Aneurisma de arco aórtico (AAAO) ? Dissecção aguda da aorta tipos I e II (DAAO I e II) Nos três grupos, a mortalidade foi significativamente inferior para pacientes operados no período após 1989. Variáveis preditivas de mortalidade para AAAS foram: complicações pulmonares (p = 0,0210), renais (p = 0,0310), neurológicas (p < 0,0001). Para DAAO I e II, a hipertensão arterial (p < 0,0001), complicações cardíacas (p < 0,0001), neurológicas (p < 0,0001), renais (p < 0,0001) e a rotura (p < 0,0001) foram preditivas de óbito, e para AAAO foram as variáveis: idade (p = 0,0001) e complicações renais (p = 0,0015). Os autores concluem que as modificações introduzidas no método de tratamento cirúrgico dos aneurismas e dissecções da aorta contribuíram significativamente para a melhora dos resultados.

Descrevemos um caso de derrame pericárdico idiopático em que, durante investigação diagnóstica, foi constatado ser um quilopericárdio. A linfografia mostrou aplasia parcial do ducto torácico. Realizamos uma breve revisão da etiopatogenia, quadro clínico, métodos diagnósticos complementares e possibilidades terapêuticas do quilopericárdio.

Background: Chagas disease is characterized by intense myocardial fibrosis stimulated by the exacerbated production of inflammatory cytokines, oxidative stress, and apoptosis. Air pollution is a serious public health problem and also follows this same path. Therefore, air pollution might amplify the inflammatory response of Chagas disease and increase myocardial fibrosis. Methods: We studied groups of Trypanosoma cruzi infected Sirius hamsters (Chagas=CH and Chagas exposed to pollution=CH+P) and 2 control groups (control healthy animals=CT and control exposed to pollution=CT+P). We evaluated acute phase (60 days post infection) and chronic phase (10 months). Echocardiograms were performed to assess left ventricular systolic and diastolic diameter, in addition to ejection fraction. Interstitial collagen was measured by morphometry in picrosirius red staining tissue. The evaluation of inflammation was performed by gene and protein expression of cytokines IL10, IFN-g, and TNF; oxidative stress was quantified by gene expression of NOX1, MnSOD, and iNOS and by analysis of reactive oxygen species; and apoptosis was performed by gene expression of BCL2 and Capsase3, in addition to TUNEL analysis. Results: Chagas groups had increased collagen deposition mainly in the acute phase, but air pollution did not increase this deposition. Also, Chagas groups had lower ejection fraction in the acute phase (p = 0.002) and again air pollution did not worsen ventricular function or dilation. The analysis of the inflammation and oxidative stress pathways were also not amplified by air pollution. Apoptosis analysis showed increased expression of BCL2 and Caspase3 genes in chagasic groups in the acute phase, with a marginal p of 0.054 in BCL2 expression among infected groups, and TUNEL technique showed amplified of apoptotic cells by pollution among infected groups. Conclusions: A possible modulation of the apoptotic pathway was observed, inferring interference from air pollution in this pathway. However, it was not enough to promote a greater collagen deposition, or worsening ventricular function or dilation caused by air pollution in this model of Chagas cardiomyopathy. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are lipid bilayer envelopes that encase several types of molecules. Their contents mostly reflect their cell origin and possible targets at other locations in the organism and can be modified in pathological conditions to interfere with intercellular communication, thus promoting disease establishment and development. These characteristics, in addition to their presence in virtually all body fluids, make such vesicles ideal for biomarker discovery in human diseases. Here, we describe the effect of different anticoagulants and the combination of two purification methods for isolation and characterization of circulating EVs from blood of chronic Chagas disease (CCD) patients. We illustrated this procedure by studying a population of patients with Chagas disease at the indeterminate chronic stage, in which the Trypanosoma cruzi is very scarce in circulation. EVs were harvested from blood collected without or with different anticoagulants. Protein and nanoparticle tracking analysis was used to measure EVs size and concentration. The EVs were purified by ultracentrifugation, followed by size‐exclusion chromatography and characterized by chemiluminescent enzyme‐linked immunosorbent assay and dot blot using antibodies that recognized parasite‐derived EVs, such as hyperimmune sera, polyclonal and monoclonal antibodies against trans‐sialidase and mucins. In parallel, antibodies against classical human EV markers CD9, CD63, CD81, and CD82, were also analyzed. The results showed that anticoagulants did not interfere with the analyzed parameters and circulating EVs from CCD patients contain T. cruzi antigens and classical human exosomal markers. Overall, our protocol is adequate for the isolation of the total circulating EVs and can serve as an important basis for further studies on biomarker discovery in Chagas' disease. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2005.02.045 Byline: Edmundo Arteaga, Aloir Queiroz Araujo, Paula Buck, Barbara Maria Ianni, Rogerio Rabello, Charles Mady Abstract: Plasma B-type natriuretic peptide (BNP) is a sensitive functional marker in heart disease including hypertrophic cardiomyopathy (HCM). The utility of plasma amino-terminal pro-BNP (NT-proBNP) quantification in heart disease has been investigated, but there are no published data regarding this test in HCM. Author Affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil Article History: Received 13 May 2004; Accepted 20 February 2005

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2004.08.021 Byline: Afonso Y. Matsumoto (a)(b), Edmundo Arteaga (a), Barbara M. Ianni (a), Ana M.F.W. Braga (a), Paula C. Buck (a), Charles Mady (a) Abstract: The aim of this study was to analyze the relationships among exercise capacity (EC), hypertrophy, and diastolic function in nonobstructive hypertrophic cardiomyopathy (NOHCM). Author Affiliation: (a) Departmnet of Cardiomyopathy, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil (b) Laboratorio Fleury, Sao Paulo, Brazil Article History: Received 29 January 2004; Accepted 22 August 2004

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2004.09.049 Byline: Edmundo Arteaga, Barbara Maria Ianni, Fabio Fernandes, Charles Mady Abstract: Selected patients with hypertrophic cardiomyopathy (HCM) have 3% to 4% annual mortality as compared to only 0.5% to 1.5% in nonselected patients. Our aim was to evaluate survival and prognostic factors in HCM in patients in a tertiary care center. Author Affiliation: Cardiomyopathy Division, University of Sao Paulo Medical School, Heart Institute (InCor), Sao Paulo, Brazil Article History: Received 13 May 2004; Accepted 20 September 2004