NOEDIR ANTONIO GROPPO STOLF
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
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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- 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.
- InsCor: um método simples e acurado para avaliação do risco em cirurgia cardíaca(2013) MEJA, Omar A. V.; LISBOA, Luiz A. F.; PUIG, Luiz B.; MOREIRA, Luiz Felipe P.; DALLAN, Luis A. O.; POMERANTZEFF, Pablo M. A.; JATENE, Fabio B.; STOLF, Noedir A. G.Background: Risk scores show difficulties to attain the same performance in different populations. Objective: To create a simple and accurate risk assessment model for patients submitted to surgery due to coronary and/or valvular disease at Instituto do Coracao da Universidade de Sao Paulo (InCor-HCFMUSP). Methods: Between 2007 and 2009, 3,000 patients were submitted to surgical procedure due to coronary artery and/or valvular disease at InCor-HCFMUSP. From this record, data of 2/3 of the patients were used for model development (bootstrap technique), and 1/3 for internal validation of the model. The performance of the model (InsCor) was compared to the 2000 Bernstein-Parsonnet (2000BP) and EuroSCORE (ES) complexes. Results: Only 10 variables were selected: age > 70 years, female sex; coronary revascularization + valve, myocardial infarction < 90 days; reoperation; surgical treatment of aortic valve; surgical treatment of tricuspid valve; creatinine < 2mg/dL; ejection fraction < 30%, and events. The Hosmer Lemeshow test for the InsCor was 0.184, indicating excellent calibration. The area under the ROC curve was 0.79 for the InsCor, 0.81 for the ES and 0.82 for 2000BP, confirming that the models are good and have similar discrimination. Conclusions: The InsCor and ES performed better than 2000BP at all stages of validation, but the new model, in addition to showing identification with the local risk factors, is simpler and more objective for mortality prediction in patients undergoing surgery due to coronary and/or valvular disease at InCor-HCFMUSP (Arq Bras Cardiol. 2013;100(3):246-254).
article 5 Citação(ões) na Scopus Long term results of septal myectomy in the treatment of obstructive hypertrophic cardiomyopathy(2011) LISBOA, Luiz Augusto Ferreira; DALLAN, Luis Alberto Oliveira; POMERANTZEFF, Pablo Maria Alberto; OLIVEIRA, Sergio Almeida de; JATENE, Fabio Biscegli; STOLF, Noedir Antonio GroppoObjectives: This study analyzed the clinical and echocardiographic late outcomes of surgical septal myectomy in patients with obstructive hypertrophic cardiomyopathy (OHCM). Methods: We examined, retrospectively, 34 consecutive adult patients (age 55.7 +/- 15.2 years) with OHCM operated on in our institution from 1988 to 2008. Only four (11.8%) patients had family history of OHCM. Nine (26.5%) patients were in New York Heart Association (NYHA) funcional class IV. Thirty (88.2%) patients had solely OHCM, and four (11.8%) had OHCM associated with coronary insufficiency. The surgical technique used in all patients was septal myectomy performed through an aortotomy. Results: In 26 (76.5%) patients the mitral insufficiency due to systolic anterior motion, decreased after the myectomy. Eight (23.5%) patients had mitral valve procedures. There was one hospitalar death (2.9%). Two (5.9%) patients required permanent pacemaker for complete heart block after the myectomy. The mean peak preoperative left ventrilcular outflow tract (LVOT) obstruction gradient was 84.9 +/- 29.0 mmHg, and decreased to 27.8 +/- 12.9 mmHg in the early postoperative and it was 19.2 +/- 11.2 mmHg in the late postoperative period (49.0 +/- 33.0 months). The NYHA functional class improved from 3.1 +/- 0.8 to 1.4 +/- 0.5 in the postoperative period. Survival free from death was 87.9% and survival free from cardiovascular events was 77.7% with mean follow-up 9.6 +/- 8.4 years. Conclusions: Surgical septal myectomy can be performed safely, with excellent survival, improvement from symptoms and relief for LVOT obstruction in patients with OHCM. The early benefits were remained at long term.- Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy(2022) BROCHET, Pauline; IANNI, Barbara Maria; LAUGIER, Laurie; FRADE, Amanda Farage; NUNES, Joao Paulo Silva; TEIXEIRA, Priscila Camillo; MADY, Charles; FERREIRA, Ludmila Rodrigues Pinto; FERRE, Quentin; SANTOS, Ronaldo Honorato Barros; KURAMOTO, Andreia; CABANTOUS, Sandrine; STEFFEN, Samuel; STOLF, Antonio Noedir; POMERANTZEFF, Pablo; FIORELLI, Alfredo Inacio; BOCCHI, Edimar Alcides; PISSETTI, Cristina Wide; SABA, Bruno; CANDIDO, Darlan da Silva; DIAS, Fabricio C.; SAMPAIO, Marcelo Ferraz; GAIOTTO, Fabio Antonio; MARIN-NETO, Jose Antonio; FRAGATA, Abilio; ZANIRATTO, Ricardo Costa Fernandes; SIQUEIRA, Sergio; PEIXOTO, Giselle De Lima; RIGAUD, Vagner Oliveira-Carvalho; BACAL, Fernando; BUCK, Paula; ALMEIDA, Rafael Ribeiro; LIN-WANG, Hui Tzu; SCHMIDT, Andre; MARTINELLI, Martino; HIRATA, Mario Hiroyuki; DONADI, Eduardo Antonio; PEREIRA, Alexandre Costa; RODRIGUES JUNIOR, Virmondes; PUTHIER, Denis; KALIL, Jorge; SPINELLI, Lionel; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChagas 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 often-fatal 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.
- Fatores de risco pré-operatórios para mediastinite após cirurgia cardíaca: análise de 2768 paciente(2012) TIVERON, Marcos Gradim; FIORELLI, Alfredo Inacio; MOTA, Eduardo Moeller; MEJIA, Omar Asdrubal Vilca; BRANDAO, Carlos Manuel de Almeida; DALLAN, Luis A. O.; POMERANTZEFF, Pablo A. M.; STOLF, Noedir A. G.Background: Longitudinal median sternotomy is the most common surgical approach for access to heart disease treatment. The deep wound infections in postoperative period of cardiovascular surgery are a serious complication requiring high costs during treatment. Different studies have indicated some risk factors for the development of mediastinitis and preoperative variables are currently under investigation. Objective: The aim of this study is to identify the preoperative risk factors for postoperative development of mediastinitis in patients undergoing coronary artery bypass grafting and valve replacement. Methods: This observational study represents a cohort of 2768 consecutive operated patients. The period considered for analysis was from May 2007 to May 2009 and there were no exclusion criteria. Analysis was performed by univariate and multivariate logistic regression model of 38 preoperative variables. Results: Thirty-five (1.3%) patients developed mediastinitis and 19 (0.7%) associated with osteomyelitis. The patient age average was 59.9 +/- 13.5 years and the EuroSCORE of 4.5 +/- 3.6. Hospital mortality was 42.8%. The multivariate analysis identified three variables as independent predictors of postoperative mediastinitis: intra-aortic balloon pump (OR 5.41, 95% CI [1.83 -16.01], P = 0.002), hemodialysis (OR 4.87, 95% CI [1.41 to 16.861, P = 0.012) and extracardiac vascular intervention (OR 4.39,95% CI [1.64 to 11.761,P = 0.003). Conclusion: This study showed that necessity of preoperative hemodynamic support with intra-aortic balloon, hemodialysis, and extracardiac vascular intervention were risk factors for development of mediastinitis after cardiac surgery.
- Long-term evolution of mitral commissurotomy in rheumatic patients with low echocardiographic score(2011) SOUZA, Luciano Rapold; BRANDAO, Carlos Manuel de Almeida; POMERANTZEFF, Pablo Maria Alberto; LEITE FILHO, Osanam Amorim; CARDOSO, Luiz Francisco; STOLF, Noedir Antonio GroppoIntroduction: The good results of open mitral commissurotomy are well known and there is a hypothesis that it could provide better results in patients selected by echocardiographic score. Objective: The purpose of this study is to analyze the late results with open mitral commissurotomy in patients selected by score and to identify variables influencing these results. Methods: From January 1990 to August 1994,50 patients were submitted to open mitral commissurotomy due to rheumatic mitral stenosis in Heart Institute of University of Sao Paulo Medical School. Patients with age < 60 years, in functional class II, III or IV (New York Heart Association) and echocardiographic score 9 were included. The mean age was 32.7 8.3 years and 41 patients (82%) were female. The functional class was II in three patients (6%), III in 46 (92%) and IV in one (2%). Forty six patients (92%) were in sinus rhythm and four (8%) were in atrial fibrillation. The mean mitral valve area was 0.9 +/- 0.2 cm(2). Results: There was no hospital mortality. There were two late deaths, one related to valve disease. Actuarial survival was 95.5 +/- 3.1 %, freedom from reoperation was 62.3 +/- 11,8% and freedom from tromboembolism was 88,2 +/- 5,0% in 18 years. There was no endocarditis. The grade of the echocardiographic score had no significant influence on the reoperations in late evolution. Conclusion: Open mitral commissurotomy presented excelent long term results in rheumatic patients with low echocardiographic score.
article 14 Citação(ões) na Scopus Os escores 2000 Bernstein-Parsonnet e EuroSCORE são similares na predição da mortalidade no Instituto do Coração-USP(2011) MEJIA, Omar Asdrubal Vilca; LISBOA, Luiz A. Ferreira; PUIG, Luiz Boro; DIAS, Ricardo Ribeiro; DALLAN, Luis A.; POMERANTZEFF, Pablo M.; STOLF, Noedir A. G.Objective: To evaluate the performance of 2000 Bernstein-Parsonnet (2000BP) and additive EuroSCORE (ES) for predicting surgical mortality at the Heart Institute, University of Sao Paulo. Methods: A prospective observational design. Seven hundred and seventy four patients were operated for coronary artery bypass graft, valve or combined procedure between May and October, 2007, were analyzed. The mortality was estimated with the 2000BP and ES. The correlation between expected mortality and observed mortality was validated through calibration and discrimination test. Results: The patients were stratified into five groups for the 2000BP and three for the ES. The Hosmer-Lemeshow test for 2000BP (P = 0.70) and for ES (P = 0.39) indicate a good calibration. The ROC curve for the 2000BP = 0.84 and for the ES = 0.81 confirms that the models are good predictors (P < 0.001). Conclusion: Both models are similar and adequate in predicting surgical mortality at the InCor-USP.- Validação do 2000 Bernstein-Parsonnet e EuroSCORE no Instituto do Coração - USP(2012) MEJIA, Omar Asdrubal Vilca; LISBOA, Luiz Augusto Ferreira; DALLAN, Luis Alberto Oliveira; POMERANTZEFF, Pablo Maria Alberto; MOREIRA, Luiz Felipe Pinho; JATENE, Fabio Biscegli; STOLF, Noedir Antonio GroppoObjective: To validate the 2000 Bernstein Parsonnet (2000BP) and additive EuroSCORE (ES) to predict mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at the Heart Institute, University of Sao Paulo (InCor/HC-FMUSP). Methods:A prospective observational design. We analyzed 3000 consecutive patients who underwent coronary bypass surgery and/or heart valve surgery, between May 2007 and July 2009 at the InCor/HC-FMUSP. Mortality was calculated with the 2000BP and ES models. The correlation between estimated mortality and observed mortality was validated by calibration and discrimination tests. Results: There were significant differences in the prevalence of risk factors between the study population, 2000BP and ES. Patients were stratified into five groups for 2000BP and three for the ES. In the validation of models, the ES showed good calibration (P = 0396), however, the 2000BP (P = 0.047) proved inadequate. In discrimination, the area under the ROC curve proved to be good for models, ES (0.79) and 2000BP (0.80). Conclusion: In the validation, 2000BP proved questionable and ES appropriate to predict mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at the InCor/HC-FMUSP.
- Experiência inicial com a técnica de Pomerantzeff para redução do tamanho do átrio esquerdo gigante(2012) SOUSA, Jocerlano Santos de; POMERANTZEFF, Pablo Maria Alberto; BRANDAO, Carlos Manuel de Almeida; GONCALVES, Lisandro Azeredo; TIVERON, Marcos Gradim; VIEIRA, Marcelo Luiz Campos; TARASOUTCHI, Flavio; STOLF, Noedir Antonio GroppoIntroduction: The most common indication for surgical correction of giant left atrium is associated with mitral valve insufficiency with or without atrial fibrillation. Several techniques for this purpose are already described with varying results. Objective: To present the initial experience with the tangential triangular resection technique (Pomerantzeff). Methods: From 2002 to 2010, four patients underwent mitral valve operation with reduction of left atrial volume by the technique of triangular resection tangential in our service. Three patients were female. The age ranged from 21 to 51 years old. The four patients presented with atrial fibrillation. Ejection fraction of left ventricle preoperatively ranged from 38% to 62%. The left atrial diameter ranged from 78mm to 140mm. After treatment of mitral dysfunction, the left atrium was reduced by resecting triangular tangential posterior wall between the pulmonary veins to avoid anatomic distortion of the mitral valve or pulmonary veins, reducing tension in the suture line. Results: Average hospital stay was 21.5 +/- 6.5 days. The mean cardiopulmonary bypass time was 130 +/- 30 minutes. There was no surgical bleeding or mortality in the postoperative period. All patients had sinus rhythm restored in the output of cardiopulmonary bypass, maintaining this rate postoperatively. The average diameter of the left atrium was reduced by 50.5% +/- 19.5%. The left ventricular ejection fraction improved in all patients. Conclusion: Initial results with this technique have shown effective reduction of the left atrium.
conferenceObject CLINICAL DIAGNOSES AND AUTOPSY FINDINGS AFTER HEART TRANSPLANTATION: DISCREPANCIES AFFECTING MANAGEMENT AND SURVIVAL - NEHTS STUDY (NECROPSY HEART TRANSPLANTATION STUDY)(2012) BOCCHI, Edimar Alcides; VALETTE, Thiago Ninck; AYUB-FERREIRA, Silvia Moreira; ISSA, Victor; BENVENUTI, Luiz Alberto; BACAL, Fernando; FIORELLI, Alfredo Inacio; CHIZZOLA, Paulo; SOUZA, Germano; POMERANTZEFF, Pablo; STOLF, NoedirBackground: Discrepancies between clinical and autopsy diagnosis of causes of death (COD) and its consequences in the management of patients were not evaluated after heart transplantation (HT). Objective: To identify discrepancies between clinical COD and autopsy results. Methods: We studied retrospectively 48 autopsies of HT receptors from 2000 to 2010 (39% of the deaths). We used the Goldman classification to study the discrepancies. Results: 31.3% missed major diagnosis with potential adverse impact on survival and that would have changed management (Class I), 2.1% missed major and minor diagnosis without potential adverse impact on survival and that would have not changed management (Class II and III), 60.4%absolute agreement (Class V), and 6,3% uncertain autopsy diagnosis (Class VI). The main discrepancies between autopsy and clinical COD and missed diagnosis were errors in the diagnosis of causes of transplanted organ dysfunction (40%), acute humoral rejection (20%), cardiac allograft disease (20%), pulmonary embolism (6.7%), disseminated intravascular coagulation (6.7%), and causes of shock (6,7%). Conclusions: This study found significant discrepancies with potential impact on therapy and outcome of HT patients. This reinforces the importance of the postmortem examination in confirming diagnostic accuracy and improving the quality of care of HT patients.