ALFREDO INACIO FIORELLI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- 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, EdecioBackground. 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.
- 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.
- 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, EdecioChagas 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.
- 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.
- Immunohistochemical Quantification of Inflammatory Cells in Endomyocardial Biopsy Fragments After Heart Transplantation: A New Potential Method to Improve the Diagnosis of Rejection After Heart Transplantation(2014) BOCCHI, E. A.; TANIGAWA, R. Y.; BRENDAO, S. M. G.; CRUZ, F.; ISSA, V.; AYUB-FERREIRA, S.; CHIZZOLA, P.; SOUZA, G.; FIORELLI, A. I.; BACAL, F.; POMERANTZEFF, P. M. A.; HONORATO, R.; LOURENCO-FILHO, D.; GUIMARAES, G.; BENVENUTI, L. A.Inconsistencies in cardiac rejection grading systems corroborate the concept that the evaluation of inflammatory intensity and myocyte damage seems to be subjective. We studied in 36 patients the potential role of the immunohistochemical (IHC) counting of inflammatory cells in endomyocardial biopsy (EMB) as an objective tool, testing the hypothesis of correlation between the International Society for Heart and Lung Transplantation 2004 rejection and IHC counting of inflammatory cells. We observed a progressive increment in CD68+ cells/mm(2) (P = .000) and CD3+ cells/mm(2) (P = .000) with higher rejection grade. A strong correlation between the grade of cellular rejection and both CD68+ cells/mm(2) and CD3+ cells/mm(2) was obtained (P =.000). One patient with CD3+ and CD68+ cells/mm(2) above the upper limit of the 95% confidence interval for cells/mm(2) found in rejection grade 1R evolved to rejection grade 2R without treatment. In patients with 2R that did not respond to treatment the values of CD68+ or CD3+ cells were higher than the overall median values for rejection grade 2R. For diagnosis of rejection needing treatment, the CD68+ and CD3+ cells/mm(2) areas under the receiver operating characteristic curves were 0.956 and 0.934, respectively. IHC counting of mononuclear inflammatory infiltrate in EMB seems to have additive potential role in evaluation of EMB for the diagnosis and prognosis of rejection episodes.