ALFREDO INACIO FIORELLI

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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

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  • article 25 Citação(ões) na Scopus
    Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy
    (2013) FRADE, Amanda Farage; TEIXEIRA, Priscila Camilo; IANNI, Barbara Maria; PISSETTI, Cristina Wide; SABA, Bruno; WANG, Lin Hui Tzu; KURAMOTO, Andreia; NOGUEIRA, Luciana Gabriel; BUCK, Paula; DIAS, Fabricio; GINIAUX, Helene; LLORED, Agnes; ALVES, Sthefanny; SCHMIDT, Andre; DONADI, Eduardo; MARIN-NETO, Jose Antonio; HIRATA, Mario; SAMPAIO, Marcelo; FRAGATA, Abilio; BOCCHI, Edimar Alcides; STOLF, Antonio Noedir; FIORELLI, Alfredo Inacio; SANTOS, Ronaldo Honorato Barros; RODRIGUES, Virmondes; PEREIRA, Alexandre Costa; KALIL, Jorge; CUNHA-NETO, Edecio; CHEVILLARD, Christophe
    Aims: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis. Methods and Results: We conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5' region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful. Conclusions: Genetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions.
  • article 1 Citação(ões) na Scopus
    Current Impact of Cardiopulmonary Bypass in Coronary Artery Bypass Grafting in Sao Paulo State
    (2020) BORGOMONI, Gabrielle Barbosa; MEJIA, Omar Asdrubal Vilca; ORLANDI, Bianca Maria Maglia; GONCHAROV, Maxim; LISBOA, Luiz Augusto Ferreira; CONTE, Pedro Henrique; OLIVEIRA, Marco Antonio Praca; FIORELLI, Alfredo Inacio; JUNIOR, Orlando Petrucci; TIVERON, Marcos Grandim; DALLAN, Luis Alberto de Oliveira; JATENE, Fabio Biscegli
    Background: Previous results on the use of cardiopulmonary bypass (CPB) have generated difficulties in choosing the best treatment for each patient undergoing myocardial revascularization surgery (CABG) in the current context. Objective: Evaluate the current impact of CPB in CABG in Sao Paulo State. Methods: A total of 2905 patients who underwent CABG were consecutively analyzed in 11 Sao Paulo State centers belonging to the Sao Paulo Registry of Cardiovascular Surgery (REPLICCAR) I. Perioperative and follow-up data were included online by trained specialists in each hospital. Associations of the perioperative variables with the type of procedure and with the outcomes were analyzed. The study outcomes were morbidity and operative mortality. The expected mortality was calculated using EuroSCORE II (ESII). The values of p <5% were considered significant. Results: There were no significant differences concerning the patients' age between the groups (p=0.081). 72.9% of the patients were males. Of the patients, 542 underwent surgery without CPB (18.7%). Of the preoperative characteristics, patients with previous myocardial infarction (p=0.005) and ventricular dysfunction (p=0.031) underwent surgery with CPB. However, emergency or New York Heart Association (NYHA) class IV patients underwent surgery without CPB (p<0.001). The ESII value was similar in both groups (p=0.427). In CABG without CPB, the radial graft was preferred (p<0.001), and in CABG with CPB the right mammary artery was the preferred one (p<0.001). In the postoperative period, CPB use was associated with reoperation for bleeding (p=0.012). Conclusion: Currently in the REPLICCAR, reoperation for bleeding was the only outcome associated with the use of CPB in CABG.
  • article 13 Citação(ões) na Scopus
    Complications after Surgical Procedures in Patients with Cardiac Implantable Electronic Devices: Results of a Prospective Registry
    (2016) SILVA, Katia Regina da; ALBERTINI, Caio Marcos de Moraes; CREVELARI, Elizabeth Sartori; CARVALHO, Eduardo Infante Januzzi de; FIORELLI, Alfredo Inacio; MARTINELLI FILHO, Martino; COSTA, Roberto
    Background: Complications after surgical procedures in patients with cardiac implantable electronic devices (CIED) are an emerging problem due to an increasing number of such procedures and aging of the population, which consequently increases the frequency of comorbidities. Objective: To identify the rates of postoperative complications, mortality, and hospital readmissions, and evaluate the risk factors for the occurrence of these events. Methods: Prospective and unicentric study that included all individuals undergoing CIED surgical procedures from February to August 2011. The patients were distributed by type of procedure into the following groups: initial implantations (cohort 1), generator exchange (cohort 2), and lead-related procedures (cohort 3). The outcomes were evaluated by an independent committee. Univariate and multivariate analyses assessed the risk factors, and the Kaplan-Meier method was used for survival analysis. Results: A total of 713 patients were included in the study and distributed as follows: 333 in cohort 1, 304 in cohort 2, and 76 in cohort 3. Postoperative complications were detected in 7.5%, 1.6%, and 11.8% of the patients in cohorts 1, 2, and 3, respectively (p = 0.014). During a 6-month follow-up, there were 58 (8.1%) deaths and 75 (10.5%) hospital readmissions. Predictors of hospital readmission included the use of implantable cardioverter-defibrillators (odds ratio [OR] = 4.2), functional class III--IV (OR = 1.8), and warfarin administration (OR = 1.9). Predictors of mortality included age over 80 years (OR = 2.4), ventricular dysfunction (OR = 2.2), functional class III-IV (OR = 3.3), and warfarin administration (OR = 2.3). Conclusions: Postoperative complications, hospital readmissions, and deaths occurred frequently and were strongly related to the type of procedure performed, type of CIED, and severity of the patient's underlying heart disease.
  • 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 7 Citação(ões) na Scopus
    Comparative experimental study of myocardial protection with crystalloid solutions for heart transplantation
    (2012) LIMA, Melchior Luiz; FIORELLI, Alfredo Inacio; VASSALLO, Dalton Valentim; PINHEIRO, Bruno Botelho; STOLF, Noedir Antonio Groppo; GOMES, Otoni Moreira
    Background: There is a growing need to improve myocardial protection, which will lead to better performance of cardiac operations and reduce morbidity and mortality. Therefore, the objective of this study was to compare the efficacy of myocardial protection solution using both intracellular and extracellular crystalloid type regarding the performance of the electrical conduction system, left ventricular contractility and edema, after being subjected to ischemic arrest and reperfusion. Methods: Hearts isolated from male Wistar (n=32) rats were prepared using Langendorff method and randomly divided equally into four groups according the cardioprotective solutions used Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1 (STH-1) and Celsior (CEL). After stabilization with KHB at 37 degrees C, baseline values (control) were collected for heart rate (HR), left ventricle systolic pressure (LVSP), maximum first derivate of rise left ventricular pressure (+dP/dt), maximum first derivate of fall left ventricular pressure (-dP/dt) and coronary flow (CF). The hearts were then perfused at 10 degrees C for 5 min and kept for 2 h in static ischemia at 20 degrees C in each cardioprotective solution. Data evaluation was done using analysis of variance in completely randomized One-Way ANOVA and Tukey's test for multiple comparisons. The level of statistical significance chosen was P<0.05. Results: HR was restored with all the solutions used. The evaluation of left ventricular contractility (LVSP, +dP/dt and -dP/dt) showed that treatment with CEL solution was better compared to other solutions. When analyzing the CF, the HTK solution showed better protection against edema. Conclusion: Despite the cardioprotective crystalloid solutions studied are not fully able to suppress the deleterious effects of ischemia and reperfusion in the rat heart, the CEL solution had significantly higher results followed by HTK>KHB>STH-1.
  • article 7 Citação(ões) na Scopus
    Sildenafil vs. Sodium Nitroprusside for the Pulmonary Hypertension Reversibility Test Before Cardiac Transplantation
    (2012) FREITAS JR., Aguinaldo Figueiredo; BACAL, Fernando; OLIVEIRA JUNIOR, Jose de Lima; FIORELLI, Alfredo Inacio; SANTOS, Ronaldo Honorato; MOREIRA, Luiz Felipe Pinho; SILVA, Christiano Pereira; MANGINI, Sandrigo; TSUTSUI, Jeane Mike; BOCCHI, Edimar Alcides
    Background: Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. Objective: This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. Methods: The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 mu g/kg/min) or SIL (100 mg, single dose). Results: Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 +/- 2.08 vs. 8.11 +/- 1.81 cm/s, p = 0.002; SNP: 6.64 +/- 1.51 vs. 7.72 +/- 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis. Conclusion: Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation. (Arq Bras Cardiol 2012;99(3):848-856)
  • article 7 Citação(ões) na Scopus
    Ruptured thoracic aortic aneurysm in patient with systemic lupus erythematosus
    (2011) CONTI, Daniel Oliveira De; DIAS, Ricardo Ribeiro; FIORELLI, Alfredo Inacio; STOLF, Noedir A. G.
    It is reported a ruptured descending thoracic aortic aneurysm in a 25-year-old systemic lupus erythematosus woman who underwent 19 years steroid therapy. She was treated with 2 endovascular stent-grafts, discharged from hospital 13 days after the procedure in good health. Three months later she returned with hemorrhagic shock due to high digestive hemorrhage secondary to an aortic-esophageal fistula. She underwent to an open emergency surgery, and died during the post-operative period.
  • article 14 Citação(ões) na Scopus
    Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model
    (2017) FIORELLI, A. I.; LOURENCO-FILHO, D. D.; TAVARES, E. R.; CARVALHO, P. O.; MARQUES, A. F.; GUTIERREZ, P. S.; MARANHAO, R. C.; STOLF, N. A. G.
    Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg.kg(-1).day(-1) orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.
  • 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 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.