NOEDIR ANTONIO GROPPO STOLF

(Fonte: Lattes)
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Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina

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  • article 22 Citação(ões) na Scopus
    Comparative Analysis of the Complications of 5347 Endomyocardial Biopsies Applied to Patients After Heart Transplantation and With Cardiomyopathies: A Single-center Study
    (2012) FIORELLI, A. I.; BENVENUTI, L.; AIELO, V.; COELHO, A. Q.; PALAZZO, J. F.; ROSSENER, R.; BARRETO, A. C. P.; MADY, C.; BACAL, F.; BOCCHI, E.; STOLF, N. A. G.
    Introduction. Endomyocardial biopsy (EMB) plays an important role in allograft surveillance to screen an acute rejection episode after heart transplantation (HT), to diagnose an unknown cause of cardiomyopathies (CMP) or to reveal a cardiac tumor. However, the procedure is not risk free. Objective. The main objective of this research was to describe our experience with EMB during the last 33 years comparing surgical risk between FIT versus no-HT patients. Method. We analyzed retrospectively the data of 5347 EMBs performed from 1978 to 2011 (33 years). For surveillance of acute rejection episodes after HT we performed 3564 (66.7%), whereas 1777 (33.2%) for CMP diagnosis, and 6 (1.0%) for cardiac tumor identification. Results. The main complications due to EMB were divided into 2 groups to facilitate analysis: major complications associated with potential death risk, and minor complications. The variables that showed a significant difference in the HT group were as follows: tricuspid Injury (.0490) and coronary fistula (.0000). Among the no-HT cohort they were insufficient fragment (.0000), major complications (.0000) and total complications (.0000). Conclusions. EMB can be accomplished with a low risk of complications and high effectiveness to diagnose CMP and rejection after HT. However, the risk is great among patients with CMP due to their anatomic characteristics. Children also constitute a risk group for EMB due to their small size in addition to the heart disease. The risk of injury to the tricuspid valve was higher among the HT group.
  • article 52 Citação(ões) na Scopus
    Myocardial Gene Expression of T-bet, GATA-3, Ror-gamma t, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed T(H)1-Type Response
    (2014) NOGUEIRA, Luciana Gabriel; SANTOS, Ronaldo Honorato Barros; FIORELLI, Alfredo Inacio; MAIRENA, Eliane Conti; BENVENUTI, Luiz Alberto; BOCCHI, Edimar Alcides; STOLF, Noedir Antonio; KALIL, Jorge; CUNHA-NETO, Edecio
    Background. Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (T(H)1/T(H)2/T(H)17/Treg) in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-gamma and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by T(H)2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-beta and IL-10) were not upregulated in CCC myocardium. Expression of T(H)1-related genes such as T-bet, IFN-gamma, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local T(H)1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-gamma production in CCC myocardium, therefore fueling inflammation.
  • article 24 Citação(ões) na Scopus
    Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy
    (2011) TEIXEIRA, Priscila Camillo; SANTOS, Ronaldo Honorato Barros; FIORELLI, Alfredo Inacio; BILATE, Angelina Morand Bianchi; BENVENUTI, Luiz Alberto; STOLF, Noedir Antonio; KALIL, Jorge; CUNHA-NETO, Edecio
    Background: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies. Methodology/Principal Findings: Myocardium homogenates from CCC (N = 5), IC (N = 5) and IDC (N = 5) patients, as well as from heart donors (N = 5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. Conclusions/Significance: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.
  • article 16 Citação(ões) na Scopus
    Tricuspid Valve Injury After Heart Transplantation Due to Endomyocardial Biopsy: An Analysis of 3550 Biopsies
    (2012) FIORELLI, A. I.; COELHO, G. H. B.; AIELLO, V. D.; BENVENUTI, L. A.; PALAZZO, J. F.; SANTOS JUNIOR, V. P.; CANIZARES, B.; DIAS, R. R.; STOLF, N. A. G.
    Introduction. Tricuspid regurgitation (TR) is the most commonly valvular dysfunction found after heart transplantation (HTx). It may be related to endomyocardial biopsy (EMB) performed for allograft rejection surveillance. Objective. This investigation evaluated the presence of tricuspid valve tissue fragments obtained during routine EMB performed after HTx and its possible effect on short-term and long-term hemodynamic status. Method. This single-center review included prospectively collected and retrospectively analyzed data. From 1985 to 2010, 417 patients underwent 3550 EMB after HTx. All myocardial specimens were reviewed to identify the presence of tricuspid valve tissue by 2 observers initially and in doubtful cases by a third observer. The echocardiographic and hemodynamic parameters were only considered for valvular functional damage analysis in cases of tricuspid tissue inadvertently removed during EMB. Results. The 417 HTx patients to 3550 EMB, including 17,550 myocardial specimens. Tricuspid valve tissue was observed in 12 (2.9%) patients corresponding to 0.07% of the removed fragments. The echocardiographic and hemodynamic parameters of these patients before versus after the biopsy showed increased TR in 2 cases (2/12; 16.7%) quantified as moderate without progression in the long term. Only the right atrial pressure showed a significant increase (P = .0420) after tricuspid injury; however, the worsening of the functional class was not significant enough in any of the subjects. Thus, surgical intervention was not required. Conclusions. Histological evidence of chordal tissue in EMB specimens is a real-world problem of relatively low frequency. Traumatic tricuspid valve injury due to EMB rarely leads to severe valvular regurgitation; only a minority of patients develop significant clinical symptoms. Hemodynamic and echocardiographic alterations are also less often observed in most patients.
  • article 82 Citação(ões) na Scopus
    MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy
    (2014) FERREIRA, Ludmila Rodrigues Pinto; FRADE, Amanda Farage; SANTOS, Ronaldo Honorato Barros; TEIXEIRA, Priscila Camillo; BARON, Monique Andrade; NAVARRO, Isabela Cunha; BENVENUTI, Luiz Alberto; FIORELLI, Alfredo Inacio; BOCCHI, Edimar Alcides; STOLF, Noedir Antonio; CHEVILLARD, Christophe; KALIL, Jorge; CUNHA-NETO, Edecio
    Background/methods: Chagas disease is caused by an intracellular parasite, Trypanosoma cruzi, and it is a leading cause of heart failure in Latin America. The main clinical consequence of the infection is the development of a Chronic Chagas disease Cardiomyopathy (CCC), which is characterized by myocarditis, hypertrophy and fibrosis and affects about 30% of infected patients. CCC has a worse prognosis than other cardiomyopathies, like idiopathic dilated cardiomyopathy (DCM). It is well established that myocardial gene expression patterns are altered in CCC, but the molecular mechanisms underlying these differences are not clear. MicroRNAs are recently discovered regulators of gene expression, and are recognized as important factors in heart development and cardiovascular disorders (CD). We analyzed the expression of nine different miRNAs inmyocardial tissue samples of CCC patients in comparison to DCM patients and samples from heart transplant donors. Using the results of a cDNA microarray database on CCC and DCM myocardium, signaling networks were built and nodal molecules were identified. Results: We observed that five miRNAs were significantly altered in CCC and three in DCM; importantly, three miRNAs were significantly reduced in CCC as compared to DCM. We observed that multiple gene targets of the differentially expressed miRNAs showed a concordant inverse expression in CCC. Significantly, most gene targets and involved networks belong to crucial disease-related signaling pathways. Conclusion: These results suggest that miRNAs may play a major role in the regulation of gene expression in CCC pathogenesis, with potential implication as diagnostic and prognostic tools.
  • article 11 Citação(ões) na Scopus
    Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients
    (2021) TEIXEIRA, Priscila Camillo; DUCRET, Axel; LANGEN, Hanno; NOGOCEKE, Everson; SANTOS, Ronaldo Honorato Barros; NUNES, Joao Paulo Silva; BENVENUTI, Luiz; LEVY, Debora; BYDLOWSKI, Sergio Paulo; BOCCHI, Edimar Alcides; TAKARA, Andreia Kuramoto; FIORELLI, Alfredo Inacio; STOLF, Noedir Antonio; POMERANZEFF, Pablo; CHEVILLARD, Christophe; KALIL, Jorge; CUNHA-NETO, Edecio
    Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.
  • article 87 Citação(ões) na Scopus
    Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10
    (2012) NOGUEIRA, Luciana Gabriel; SANTOS, Ronaldo Honorato Barros; IANNI, Barbara Maria; FIORELLI, Alfredo Inacio; MAIRENA, Eliane Conti; BENVENUTI, Luiz Alberto; FRADE, Amanda; DONADI, Eduardo; DIAS, Fabricio; SABA, Bruno; WANG, Hui-Tzu Lin; FRAGATA, Abilio; SAMPAIO, Marcelo; HIRATA, Mario Hiroyuki; BUCK, Paula; MADY, Charles; BOCCHI, Edimar Alcides; STOLF, Noedir Antonio; KALIL, Jorge; CUNHA-NETO, Edecio
    Background: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.
  • article 4 Citação(ões) na Scopus
    Successful Endomyocardial Biopsy Guided by Transthoracic Two-Dimensional Echocardiography
    (2011) FIORELLI, A. I.; COELHO, G. B.; SANTOS, R. H. B.; OLIVEIRA JR., J. L.; AIELO, V.; BENVENUTI, L.; OLIVEIRA, A. S.; SILVA, M. A. F. Da; CHIZZOLA, P. R.; COSTA, R.; MATHIAS JR., W.; BACAL, F.; BOCCHI, E. A.; STOLF, N. A. G.
    Introduction. Two-dimensional (2-D) echocardiography is an excellent alternative method to perform endomyocardial biopsies (EB) in special situations, mainly when the patient is in a critical state and cannot go to the catheterization laboratory or when there are contraindications to the use of fluoroscopy as in the pregnancy. Objective. This single-center experience analyzed the last 25 years use of an EB technique guided by echocardiography realized at the bedside on critical patients. Methods. From 1985 to 2010, we performed 76 EB guided by 2-D echocardiography on 59 patients, among whom 38 (64.4%) were critically ill with examinations at the bedside; among 10 (16.9%) subjects, the procedure was carried out simultaneously with fluoroscopy for safety's sake during the learning period. In addition, 8 (13.6%) were unavailable for fluoroscopy, and 3 (5.1%) required a hybrid method due to an intracardiac tumor. Results. The main adverse effects included local pain (n = 4, 5.6%); difficult out successful puncture due to previous biopsies (n = 4, 5.6%); local hematoma without major consequences (n = 3, 4.2%); failed but ultimately successful puncture on the first try due to previous biopsies or (n = 3, 4.2%); obesity and immediate postoperative period with impossibility to pass the bioptome into the right ventricle; however 2 days later the procedure was repeated successfully by echocardiography (n = 1, 1.4%). All myocardial specimens displayed suitable size. There were no undesirable extraction effects on the tricuspid valve tissue. In this series, there was no case of death, hemopericardium, or other major complication as a direct consequence of the biopsy. Conclusion. 2-D echocardiography is a special feature to guide EB is mainly in critically ill patients because it can be performed at the bedside without additional risk or disadvantages of fluoroscopy. The hybrid method associating 2-D echocardiography and fluoroscopy allows the procedure in different situations such as intracardiac tumor cases.
  • article 2 Citação(ões) na Scopus
    Estudo experimental comparativo do enxerto homólogo pulmonar tratado pelo processo L-Hydro com o homoenxerto pulmonar a fresco
    (2011) REY, Nei Antonio; MOREIRA, Luiz Felipe Pinho; CHEUNG, David T.; CASAGRANDE, Ivan Sergio Joviano; BENVENUTI, Luiz Alberto; STOLF, Noedir Antonio Groppo
    Objective: In an effort to make available homografts preserved in a simpler and less costly way, we evaluated the polyethyleneglycol, L-Hydro (LH) method, that consists in the controlled extraction of antigenic substances and the incorporation of anti-inflammatory and anti-thrombotic agent. Methods: We substituted the pulmonary trunk in ten ovines, seven received LH treated pulmonary homografts and three, fresh pulmonary homografts, orthotopically implanted and followed-up for 320 days. Ovines where evaluated by means of laboratory tests, echocardiographic exams. At the 320 days, were euthanized, hemodynamic, radiology, macroscopic, optic/electronic microscopic, scanning/transmission evaluations were performed. Results were analyzed by Student t test of independent samples for continuous data, by variance analysis of repeated measures, and by Fisher exact test for categorical data. Results: We couldn't establish relevant differences in clinical evolution and laboratory tests between groups. Echocardiogram revealed difference in pulmonary medium gradient, which was significant 10 months follow-up, higher in the control group. Radio logic and macroscopic evaluations didn't established differences. In the optic/electronic microscopic evaluation, liner and interstitial cells were equally found in both groups. The cell liner percent calculated in both groups was similar. Cellularity nodules were observed only infresh homograft group. Conclusions: These data indicate that both groups presented similar clinical/hemodynamic performances. The LH group's echocardiogram presented a better performance. It also presented histological evidences of interstitial and endothelial cell repopulation. In the macro/optic and electronic microscopic analysis, group L-H presented macroscopy/histological structure and ultra-structural similar to the fresh group, with the exception of nodules with higher interstitial cellularity, present only in the fresh homograft group.
  • article 6 Citação(ões) na Scopus
    Cavo-pulmonary anastomosis associated with left ventricular in comparison with biventricular circulatory support in acute heart failure
    (2012) SANTOS, Luis Alberto Saraiva; BENICIO, Anderson; MATTOS JUNIOR, Ewaldo de; BENVENUTTI, Luiz Alberto; CESTARI, Idagene Aparecida; STOLF, Noedir Antonio Groppo; MOREIRA, Luiz Felipe Pinho
    Objective: Right ventricular (RV) failure during left ventricular assist device (LVAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavo-pulmonary anastomosis on LVAD performance and RV myocardial compromise in comparison with biventricular circulatory support, in a model of biventricular failure. Methods: LVAD support was performed by centrifugal pump in 21 pigs with severe biventricular failure obtained by FV induction. Animals were randomized to be submitted to cavo-pulmonary anastomosis, to biventricular circulatory support or to control group. They were maintained under circulatory support and hemodynamic monitoring for 3h. Venous lactate and cytokines serum levels were also obtained. Endocardium samples were analyzed by electronic microscopy. Results: FV maintenance was responsible for acute LVAD impairment after 180 min in the control group. cavo-pulmonary anastomosis resulted in non-significant improvement of LVAD pump flow in relation to control group (+55 +/- 14 ml/kg/min, P=0.072), while animals under biventricular support maintained higher LVAD flow (+93 +/- 17 ml/kg/min, P=0.012). Mean arterial pressure remained constant only in biventricular group (P<0.001), which also presented decrease of right atrial and ventricular pressures. Similar increases in lactate and cytokines levels were observed in the three groups. Ultra-structural analysis documented low levels of myocardial swelling in the biventricular group (P=0.017). Conclusion: The concomitant use of cavo-pulmonary anastomosis during LVAD support in a pig model of severe biventricular failure resulted in non-significant improvement of hemodynamic performance and it did not effectively replace the use of biventricular support.