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Journal of the American College of Cardiology | 2010

Prognostic Significance of Myocardial Fibrosis Quantification by Histopathology and Magnetic Resonance Imaging in Patients With Severe Aortic Valve Disease

Clerio F. Azevedo; Marcelo Nigri; Maria de Lourdes Higuchi; Pablo Maria Alberto Pomerantzeff; Guilherme Sobreira Spina; Roney Orismar Sampaio; Flávio Tarasoutchi; Max Grinberg; Carlos Eduardo Rochitte

OBJECTIVES We sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement. BACKGROUND Severe aortic valve disease is characterized by progressive accumulation of interstitial MF. METHODS Fifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27+/-22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52+/-17 months to evaluate long-term survival. RESULTS There was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r=0.69, p<0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r=-0.42, p=0.04 for histopathology; r=-0.47, p=0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square=6.32, p=0.01 for histopathology; chi-square=5.85, p=0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality. CONCLUSIONS The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease.


Journal of the American College of Cardiology | 2003

Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology.

Flávio Tarasoutchi; Max Grinberg; Guilherme Sobreira Spina; Roney Orismar Sampaio; L.uís F. Cardoso; Eduardo Giusti Rossi; Pablo Maria Alberto Pomerantzeff; Francisco R.M. Laurindo; Protásio Lemos da Luz; José Antonio Franchini Ramires

OBJECTIVES This study was designed to assess the feasibility and the long-term results of a symptom-based strategy of aortic valve replacement in a Brazilian population with predominant rheumatic etiology. BACKGROUND Optimal criteria for valve replacement in aortic regurgitation (AR) are still not entirely clear. The appearance of symptoms is an indication for surgery, but may be associated with myocardial damage. Although cardiac imaging data have provided a safer guide for such decisions, the use of symptom-based surgical indication has not been validated and might conceivably be better in populations with predominant rheumatic etiology and younger age. METHODS Echocardiography and rest-exercise radionuclide ventriculography were performed in 75 patients with severe AR, age 28 +/- 9 years, over a period of 10 +/- 0.69 years. Thirty-seven patients developed symptoms and underwent aortic valve replacement surgery within six months. Thirty-eight patients remained asymptomatic and were managed medically. RESULTS Survival was 100% in asymptomatic patients and 82% in symptomatic. Surgical treatment caused marked ventricular remodeling, with ventricular diameter involution and an improvement of rest-exercise ejection fraction percent variation. Multivariate analysis showed that the probability of developing symptoms within 10 years was 58% for a patient with a left ventricular end-diastolic diameter > or =70 mm and 76% for a patient with left ventricular end-systolic (LVESD) > or =50 mm. Logistic regression identified LVESD and age as the most predictive and specific, but not sensitive, indicators of symptom development. CONCLUSIONS Application of a standardized therapeutic strategy to patients with severe AR and predominant rheumatic etiology resulted in 90.6% survival after 10 years of follow-up.


American Heart Journal | 2009

Contrast-enhanced magnetic resonance imaging identifies focal regions of intramyocardial fibrosis in patients with severe aortic valve disease: Correlation with quantitative histopathology.

Marcelo Nigri; Clerio F. Azevedo; Carlos Eduardo Rochitte; Vladimir Schraibman; Flávio Tarasoutchi; Pablo M. Pommerantzeff; Carlos Manuel de Almeida Brandão; Roney Orismar Sampaio; José Rodrigues Parga; Luiz Francisco Rodrigues de Ávila; Guilherme Sobreira Spina; Max Grinberg

BACKGROUND Chronic aortic valve disease (AVD) is characterized by progressive accumulation of interstitial myocardial fibrosis (MF). However, assessment of MF accumulation has only been possible through histologic analyses of endomyocardial biopsies. We sought to evaluate contrast-enhanced magnetic resonance imaging (ce-MRI) as a noninvasive method to identify the presence of increased MF in patients with severe AVD. METHODS Seventy patients scheduled to undergo aortic valve replacement surgery were examined by cine and ce-MRI in a 1.5-T scanner. Cine images were used for the assessment of left ventricular (LV) volumes, mass, and function. Delayed-enhancement images were used to characterize the regions of MF. In addition, histologic analyses of myocardial samples obtained during aortic valve replacement surgery were used for direct quantification of interstitial MF. Ten additional subjects who died of noncardiac causes served as controls for the quantitative histologic analyses. RESULTS Interstitial MF determined by histopathologic analysis was higher in patients with AVD than in controls (2.7% +/- 2.0% vs 0.6% +/- 0.2%, P = .001). When compared with histopathologic results, ce-MRI demonstrated a sensitivity of 74%, a specificity of 81%, and an accuracy of 76% to identify AVD patients with increased interstitial MF. There was a significant inverse correlation between interstitial MF and LV ejection fraction (r = -0.67, P < .0001). Accordingly, patients with identifiable focal regions of MF by ce-MRI exhibited worse LV systolic function than those without MF (45% +/- 14% vs 65% +/- 14%, P < .0001). CONCLUSIONS Contrast-enhanced MRI allows for the noninvasive detection of focal regions of MF in patients with severe AVD. Moreover, patients with identifiable MF by ce-MRI exhibited worse LV functional parameters.


Arquivos Brasileiros De Cardiologia | 2009

Perfil neuro-hormonal de pacientes reumáticos com insuficiência aórtica crônica importante

Guilherme Sobreira Spina; Flávio Tarasoutchi; Roney Orismar Sampaio; Marcelo Luiz Campos Vieira; Celia Strunz; Francisco Rafael Martins Laurindo; Max Grinberg

BACKGROUND Neurohormones are involved in the physiopathology of heart failure, but little is known about its behavior in significant chronic aortic regurgitation (AR). We aimed at analyzing the behavior of these mediators in AF. OBJECTIVE We aimed at analyzing the behavior of these mediators in AF. METHODS We analyzed 89 patients with AF, whose mean age was 33.6+/-11.5 years and of whom 84.6% were males, 60% asymptomatic, all with rheumatic etiology. After the clinical and echocardiographic assessment, plasma measurements of tumor necrosis factor (TNF), soluble TNF receptor types I and II (sTNFRI e sTNFRII), interleukin-6 (IL-6), its soluble receptor (sIL6R), endothelin-1 and B-type natriuretic peptide (BNP) were carried out; 12 healthy individuals were used as controls. RESULTS The mean values of the left ventricle diastolic diameter (LVDD) were 71.9+/-8.3mm, whereas the mean values of the LV systolic diameter (LVSD) were 50.4+/-9.3mm. The neurohormonal levels were elevated in patients with AF (TNF 92.65+/-110.24 pg/mL vs. 1.67+/-1.21 pg/ml in controls, p<0.001), (IL-6 7.17+/-7.78 pg/ml vs. 0.81+/-0.38 pg/mL in controls, p=0.0001) and TNFRI (894.75+/-348.87 pg/mL vs. 521.42+/-395.13 pg/ml, p=0.007). Except for the BNP levels, symptomatic and asymptomatic patients presented a similar neurohormonal profile. There was a correlation between TNFRII and LVDD (r=-0.329, p=0.038) and LVSD (r=-0.352, p=0.027). BNP levels were significantly higher in symptomatic patients and only in the latter it was possible to establish a correlation between BNP and ventricular diameters. CONCLUSION Patients with significant chronic AF present high neurohormonal levels, with no correlation with the symptomatic status. The TNFRII and BNP levels could be correlated with ventricular diameters, but only the latter could be correlated with symptoms.FUNDAMENTO: Os neuro-hormonios estao envolvidos na fisiopatologia da insuficiencia cardiaca, mas pouco se sabe sobre seu comportamento na insuficiencia aortica cronica importante (IAo). OBJETIVO: Analisar o comportamento desses mediadores na IAo. METODOS: Analisamos 89 pacientes com IAo, com media etaria de 33,6±11,5 anos, 84,6% do sexo masculino, 60% assintomaticos, todos de etiologia reumatica. Apos avaliacao clinica e ecocardiografica, realizaram-se dosagens plasmaticas de fator de necrose tumoral (TNF), seus antagonistas receptores soluveis tipos I e II (sTNFRI e sTNFRII), interleucina-6 (IL-6), seu receptor soluvel, endotelina-1 e peptideo natriuretico tipo B (BNP). Doze individuos saudaveis serviram como controle. RESULTADOS: O valor medio de diâmetro diastolico (DD) do ventriculo esquerdo (VE) foi de 71,9±8,3 mm, e o do diâmetro sistolico (DS) do VE, de 50,4±9,3 mm. Os niveis de neuro-hormonios estavam elevados nos pacientes com IAo: TNF 92,65±110,24 pg/ml vs. 1,67±1,21 pg/ml nos controles, p<0,001; IL-6 7,17±7,78 pg/ml vs. 0,81±0,38 pg/ml nos controles, p = 0,0001; e TNFRI 894,75±348,87 pg/ml vs. 521,42±395,13 pg/ml, p = 0,007. Com excecao dos niveis de BNP, os pacientes sintomaticos e assintomaticos apresentaram perfil neuro-hormonal semelhante. Houve correlacao entre TNFRII e diâmetro diastolico do ventriculo esquerdo (DDVE) (r = -0,329, p = 0,038) e diâmetro sistolico do ventriculo esquerdo (DSVE) (r = -0,352, p = 0,027). Os niveis de BNP estavam significativamente mais altos em pacientes sintomaticos, e apenas nestes foi possivel correlacao entre BNP e diâmetros ventriculares. CONCLUSAO: Pacientes com insuficiencia aortica cronica importante apresentam altos niveis neuro-hormonios, sem correlacao com o status sintomatico. Os niveis de TNFRII e BNP puderam ser correlacionados com diâmetros ventriculares, mas apenas este ultimo com sintomas.


Inflammation | 2013

CXCL9/Mig Mediates T cells Recruitment to Valvular Tissue Lesions of Chronic Rheumatic Heart Disease Patients

Kellen Christina Faé; Selma A. Palacios; Luciana G. Nogueira; Sandra E. Oshiro; Léa Maria Macruz Ferreira Demarchi; Angelina M. Bilate; Pablo Maria Alberto Pomerantzeff; Carlos Rodrigues Brandão; Petronio G. Thomaz; Maxwell dos Reis; Roney Orismar Sampaio; Ana Cristina d'Andretta Tanaka; Edecio Cunha-Neto; Jorge Kalil; Luiza Guilherme

Rheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection frequently observed in infants from developing countries. Rheumatic heart disease (RHD), the major sequel of RF, leads to chronic inflammation of the myocardium and valvular tissue. T cells are the main population infiltrating cardiac lesions; however, the chemokines that orchestrate their recruitment are not clearly defined. Here, we investigated the expression of chemokines and chemokine receptors in cardiac tissue biopsies obtained from chronic RHD patients. Our results showed that CCL3/MIP1α gene expression was upregulated in myocardium while CCL1/I-309 and CXCL9/Mig were highly expressed in valvular tissue. Auto-reactive T cells that infiltrate valvular lesions presented a memory phenotype (CD4+CD45RO+) and migrate mainly toward CXCL9/Mig gradient. Collectively, our results show that a diverse milieu of chemokines is expressed in myocardium and valvular tissue lesions and emphasize the role of CXCL9/Mig in mediating T cell recruitment to the site of inflammation in the heart.


Revista Da Sociedade Brasileira De Medicina Tropical | 1995

Estudo retrospectivo de latrodectismo na Bahia, Brasil

Rejâne Maria Lira-da-Silva; Graciela Brige Matos; Roney Orismar Sampaio; Tania Brazil Nunes

This work is a retrospective study of latrodectism in the State of Bahia, Brazil, from August 1980 to July 1990. The data concerning the accidents were obtained from file cards at the Antivenom Information Center of Bahia (AVICB). Latrodectus curacavienis was the ethiologic agent identified in 28% of the arachnid accidents. The major incidence was registered in urban area (57%) affecting men (70%) more than women, with 10 to 29year-old age group (58%). Local pain (56%), erythematous papula (29%) and light oedema (17%) were the principal local symptoms. Pain in the limbs (29%), tremor and rigidities (29%), sweating (28%), limbs and arms paresthesia (21%) and abdominal pain (17%) were systemic ones. The treatment was mainly symptomatic (67%) and antivenin serum was used in 21% of the cases. After serotherapy, 64% of the patients left the hospital within less than 24 hours.


American Journal of Cardiology | 2011

Comparison of Inhaled Nitric Oxide Versus Oxygen on Hemodynamics in Patients With Mitral Stenosis and Severe Pulmonary Hypertension After Mitral Valve Surgery

Juliano L. Fernandes; Roney Orismar Sampaio; Carlos Manuel de Almeida Brandão; Tarso Augusto Duenhas Accorsi; Luiz Francisco Cardoso; Guilherme Sobreira Spina; Flávio Tarasoutchi; Pablo Maria Alberto Pomerantzeff; José Otávio Costa Auler; Max Grinberg

Pulmonary hypertension represents an important cause of morbidity and mortality in patients with mitral stenosis who undergo cardiac surgery, especially in the postoperative period. The aim of this study was to test the hypothesis that inhaled nitric oxide (iNO) would improve the hemodynamic effects and short-term clinical outcomes of patients with mitral stenosis and severe pulmonary hypertension who undergo cardiac surgery in a randomized, controlled study. Twenty-nine patients (4 men, 25 women; mean age 46 ± 2 years) were randomly allocated to receive iNO (n = 14) or oxygen (n = 15) for 48 hours immediately after surgery. Hemodynamic data, the use of vasoactive drugs, duration of stay, and short-term complications were assessed. No differences in baseline characteristics were observed between the groups. After 24 and 48 hours, patients receiving iNO had a significantly greater increase in cardiac index compared to patients receiving oxygen (p <0.0001). Pulmonary vascular resistance was also more significantly reduced in patients receiving iNO versus oxygen (-117 dyne/s/cm(5), 95% confidence interval -34 to -200, vs 40 dyne/s/cm(5), 95% confidence interval -34 to 100, p = 0.005) at 48 hours. Patients in the iNO group used fewer systemic vasoactive drugs (mean 2.1 ± 0.14 vs 2.6 ± 0.16, p = 0.046) and had a shorter intensive care unit stay (median 2 days, interquartile range 0.25, vs median 3 days, interquartile range 7, p = 0.02). In conclusion, iNO immediately after surgery in patients with mitral stenosis and severe pulmonary hypertension improves hemodynamics and may have short-term clinical benefits.


Revista Da Sociedade Brasileira De Medicina Tropical | 2008

Endocardite por Coxiella burnetii (febre Q): doença rara ou pouco diagnosticada? Relato de caso

Rinaldo Focaccia Siciliano; Henrique Barbosa Ribeiro; Remo Holanda de Mendonça Furtado; Jussara Bianchi Castelli; Roney Orismar Sampaio; Fabiana Cristina Pereira dos Santos; Silvia Colombo; Max Grinberg; Tânia Mara Varejão Strabelli

Q fever is a zoonosis of worldwide distribution that is caused by Coxiella burnetii. However, reports of this disease in Brazil are rare. Seroepidemiological studies have shown relatively high frequencies of antibodies against Coxiella burnetii in populations with occupational exposure. In humans, it can be manifested clinically as acute or chronic disease. Endocarditis is the most frequent chronic form of Q fever and the form with the greatest morbidity and mortality. We report a severe case of endocarditis due to Coxiella burnetii acquired in Brazil that had a fatal outcome, despite specific antibiotic therapy and valve surgery treatment.


Arquivos Brasileiros De Cardiologia | 2009

Sangramento durante a anticoagulação oral: alerta sobre um mal maior

Paulo de Lara Lavítola; Guilherme Sobreira Spina; Roney Orismar Sampaio; Flávio Tarasoutchi; Max Grinberg

BACKGROUND Bleeding is one of the main concerns in patients undergoing oral anticoagulation therapy. OBJECTIVE To investigate the determinant causes of bleeding in patients undergoing oral anticoagulant therapy. METHODS A total of 360 patients with atrial fibrillation (AF) undergoing oral anticoagulant (ACo) therapy, with a target INR of 2.0-3.5, were followed prospectively for a period of 48 +/- 7.2 months. The patients were evaluated on average every 30 days and were investigated regarding the presence of associated pathology that could lead to bleeding. RESULTS A total of 338 patients participated in the present study. Of these, 210 (62.13%) were females. Mitral stenosis was present in 218 patients (64.4%), a mitral biological prosthesis in 64 (18.9%) and mitral valve failure in 56 (16.5%) patients. Bleeding occurred in 65 patients (19.2%), being severe in 7 (10%) patients. In 38/65 patients, a new associated disease was identified, which facilitated bleeding. An associated disease was identified in 100% of the patients with bleeding within the therapeutic range, against 49.05% of associated disease diagnosis in those with an INR > 3.5 (p=0.001). CONCLUSION The diagnosis of a local disease associated to the bleeding was frequent among those patients undergoing oral anticoagulant therapy (58.5%). There was an association between bleeding with an INR within the therapeutic range (INR=2.0-3.5) and the diagnosis of a pathology predisposing to bleeding (p<0.001). It is mandatory to investigate the cause of bleeding in patients undergoing oral anticoagulant therapy, especially if the INR is within the therapeutic range.FUNDAMENTO: Sangramento e uma das grandes preocupacoes em pacientes sob anticoagulacao oral. OBJETIVO: Investigar causas determinantes do sangramento em usuarios de anticoagulante oral. METODOS: Foram acompanhados prospectivamente, por 48 ± 7,2 meses, 360 pacientes com fibrilacao atrial (FA), todos em uso de anticoagulante oral (ACo) com INR-alvo de 2,0-3,5, avaliados em media a cada 30 dias. Os pacientes foram investigados quanto a presenca de patologia associada que levasse a sangramento. RESULTADOS: Participaram deste estudo 338 pacientes. Desses, 210 (62,13%) eram do sexo feminino. A estenose mitral estava presente em 218 pacientes (64,4%), a protese biologica mitral em 64 (18,9%) e a insuficiencia da valva mitral em 56 (16,5%). O sangramento ocorreu em 65 pacientes (19,2%) e de forma grave em 7 (10%). Em 38/65 pacientes (58,5%), identificou-se nova doenca associada, facilitadora do sangramento. Em 100% dos pacientes com sangramento na faixa terapeutica, foi encontrada doenca associada, contra 49,05% de diagnostico de doencas associadas naqueles com INR > 3,5 (p = 0,001). CONCLUSAO: O diagnostico de doenca local associada ao sangramento foi frequente entre os medicados com anticoagulante oral (58,5%). Houve associacao entre sangramento com INR na faixa terapeutica (INR 2,0-3,5) e diagnostico de patologia predisponente a sangramento (p < 0,001). Em pacientes em uso de anticoagulante oral que apresentam sangramento, e mandatoria a investigacao da causa, sobretudo se a INR estiver na faixa terapeutica.


Arquivos Brasileiros De Cardiologia | 2004

Troca valvar com preservação de cordas e plástica na cirurgia da insuficiência mitral crônica

José Luiz Dancini; Pablo Maria Alberto Pomerantzeff; Guilherme Sobreira Spina; Mirian Magalhães Pardi; Maria Clementina Pinto Giorgi; Roney Orismar Sampaio; Max Grinberg; Sérgio Almeida de Oliveira

OBJECTIVE To compare, from the clinical and laboratory points of view, 3 groups of patients undergoing surgical treatment for isolated chronic mitral insufficiency. One group underwent valvuloplasty, and the other 2 groups underwent mitral valve replacement with different techniques for chordal preservation. METHODS Twenty-eight patients with a mean age of 54.1 years, no coronary or multivalvular disease, and no reoperation, underwent surgery as follows: 9 underwent valvuloplasty; 10 underwent mitral valve replacement with chordal preservation in both leaflets; and 9 underwent mitral valve replacement with chordal preservation only in the posterior leaflet. Clinical, Doppler echocardiographic, and radionuclide ventriculographic assessments were performed until the 6th month of follow-up. RESULTS At the end, 88.8% of the patients were in functional class I. One died due to intracranial hemorrhage during anticoagulant treatment. The left ventricular diastolic diameter (P<0.0001) and end-diastolic volume (P<0.0001) decreased in the 3 groups. Only the patients undergoing valvuloplasty had a decrease in systolic diameter (P=0.0003) and in end-systolic volume (P=0.0040), with no change in the ejection fraction (P=0.5586). The patients undergoing mitral valve replacement had a similar drop in ejection fraction (P=0.0001 and P=0.0296). CONCLUSION The 3 surgical techniques used provided clinical improvement. Patients undergoing valvuloplasty had better preservation of ventricular function. No significant difference was observed in cardiac performance between the 2 groups undergoing mitral valve replacement with chordal preservation within a 6-month follow-up.

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Max Grinberg

University of São Paulo

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Nelson Elias

University of São Paulo

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