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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 [...]

BACKGROUND: Familial aggregation of Chagas cardiac disease in T. cruzi-infected persons suggests that human genetic variation may be an important determinant of disease progression. OBJECTIVE: To perform a GWAS using a well-characterized cohort to detect single nucleotide polymorphisms (SNPs) and genes associated with cardiac outcomes. METHODS: A retrospective cohort study was developed by the NHLBI REDS-II program in Brazil. Samples were collected from 499 T. cruzi seropositive blood donors who had donated between 1996 and 2002, and 101 patients with clinically diagnosed Chagas cardiomyopathy. In 2008-2010, all subjects underwent a complete medical examination. After genotype calling, quality control filtering with exclusion of 20 cases, and imputation of 1,000 genomes variants; association analysis was performed for 7 cardiac and parasite related traits, adjusting for population stratification. RESULTS: The cohort showed a wide range of African, European, and modest Native American admixture proportions, consistent with the recent history of Brazil. No SNPs were found to be highly (P

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.

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]