Wilson de Oliveira

II Consenso Brasileiro em Doença de Chagas, 2015

Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.

2 nd Brazilian Consensus on Chagas Disease, 2015

Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research .

Cell Therapy in Chagas Cardiomyopathy (Chagas Arm of the Multicenter Randomized Trial of Cell Therapy in Cardiopathies Study) A Multicenter Randomized Trial

Background —Previous studies suggested that transplantation of autologous bone marrow derived mononuclear cells (BMNC) improves heart function in chronic chagasic cardiomyopathy (CCC). We report the results of the first randomized trial of BMNC therapy in CCC. Methods and Results —Patients aged 18-75 years with CCC, NYHA class III or IV, LVEF less than 35%, and optimized therapy were randomized to intracoronary injection of autologous BMNC or placebo. Primary endpoint was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5%. Between July 2005 and October 2009 234 patients were enrolled. Two abandoned the study and 49 were excluded due to protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had trimmed mean age of 52.4 years (50.8 to 54.0) and LVEF of 26.1% (25.1 to 27.1) at baseline. Median number of injected BMNCs was 2.20 x 108 (1.40-3.50 x 108). Change in LVEF did not differ significantly between treatment groups: trimmed mean ΔEF= 3.0 (1.3 to 4.8) for BMNC and 2.5 (0.6 to 4.5) for placebo (p=0.519) at 6 months; ΔEF= 3.5 (1.5 to 5.5) for BMNC and ΔEF= 3.7 (1.5 to 6.0) for placebo (p=0.850) at 12 months. Left ventricular systolic and diastolic volumes, NYHA class, Minnesota life quality questionnaire, BNP concentrations, and 6-min walking test did also not differ between groups. Conclusions —Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with CCC. Clinical Trial Registration Information —ClinicalTrials.gov; Identifier: [NCT00349271][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00349271&atom=%2Fcirculationaha%2Fearly%2F2012%2F04%2F19%2FCIRCULATIONAHA.111.067785.atomBackground— Previous studies suggested that transplantation of autologous bone marrow–derived mononuclear cells (BMNCs) improves heart function in chronic chagasic cardiomyopathy. We report the results of the first randomized trial of BMNC therapy in chronic chagasic cardiomyopathy. Methods and Results— Patients 18 to 75 years of age with chronic chagasic cardiomyopathy, New York Heart Association class II to IV heart failure, left ventricular ejection fraction (LVEF) <35, and optimized therapy were randomized to intracoronary injection of autologous BMNCs or placebo. The primary end point was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5. Between July 2005 and October 2009, 234 patients were enrolled. Two patients abandoned the study and 49 were excluded because of protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had a trimmed mean age of 52.4 years (range, 50.8–54.0 years) and LVEF of 26.1 (range, 25.1–27.1) at baseline. Median number of injected BMNCs was 2.20×108 (range, 1.40–3.50×108). Change in LVEF did not differ significantly between treatment groups: trimmed mean change in LVEF at 6 months, 3.0 (1.3–4.8) for BMNCs and 2.5 (0.6–4.5) for placebo (P=0.519); change in LVEF at 12 months, 3.5 (1.5–5.5) for BMNCs and 3.7 (1.5–6.0) for placebo (P=0.850). Left ventricular systolic and diastolic volumes, New York Heart Association functional class, Minnesota quality-of-life questionnaire, brain natriuretic peptide concentrations, and 6-minute walking test did also not differ between groups. Conclusion— Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with chronic chagasic cardiomyopathy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00349271.

All-around care for patients with Chagas disease: a challenge for the XXI century

In 1987, the University of Pernambucos Oswaldo Cruz Hospital in Recife, Brazil opened its Chagas Disease and Heart Failure Outpatient Clinic with the aim of providing its patients all-around care through adoption of a biopsychosocial model of care. All-around care involves caring for the patient as a whole human being in the context of the biological, psychological and social factors present, which are an inherent part of the human condition. One prerequisite for the proposed model of care is the participation of a multidisciplinary team of trained technical staff committed to this framework. Although the main focus of the service is on care, teaching and research are also an important part of its work. The Pernambuco Association of Chagas Disease Patients is guided by the same model of care and has been carrying out educational activities relating to the disease, its treatment and support for patients and family members for several years. This Association plays an important role in advocating to public authorities on behalf of patients. The accumulated experience of the past 22 years has shown us that a broad vision of health care can help clinicians and policy makers to make decisions that are more in tune with the everyday reality of the patient, which in turn has a positive impact on adherence to treatment and quality of life.

Chest wall regional volume in heart failure patients during inspiratory loaded breathing.

Were evaluated individuals divided into two groups: we studied chronic heart failure (CHF) (19 patients with CHF plus cardiomegaly) and control (12 healthy volunteers) during performance of inspiratory loaded breathing (ILB). We evaluated: spirometry, functional capacity through the six-minute walk test (6MWT), and distribution of thoracoabdominal volumes via optoelectronic plethysmography (OEP), namely volume variations of pulmonary rib cage (Vrc,p), abdominal rib cage (Vrc,a), and abdomen (Vab). In each compartment, the percentage contributions of right and left sides were also calculated. During ILB, patients with heart failure were characterized by a significant reduction of the Vrc,a volume variations compared to the control group. Correlations were found between left %Vrc,a on the left side measured during ILB and left ventricular ejection fraction (r=0.468; p=0.049), and dyspnea after the 6MWT (r=-0.878; p<0.01).Then, patients with CHF and cardiomegaly are characterized by a reduced mobility in left part of the lower part of the rib cage, that contributes leading to increased perception of dyspnea during submaximal exercise.

Cell Therapy in Chagas Cardiomyopathy (Chagas Arm of the MiHeart Study): A Multicenter Randomized Trial

Background —Previous studies suggested that transplantation of autologous bone marrow derived mononuclear cells (BMNC) improves heart function in chronic chagasic cardiomyopathy (CCC). We report the results of the first randomized trial of BMNC therapy in CCC. Methods and Results —Patients aged 18-75 years with CCC, NYHA class III or IV, LVEF less than 35%, and optimized therapy were randomized to intracoronary injection of autologous BMNC or placebo. Primary endpoint was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5%. Between July 2005 and October 2009 234 patients were enrolled. Two abandoned the study and 49 were excluded due to protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had trimmed mean age of 52.4 years (50.8 to 54.0) and LVEF of 26.1% (25.1 to 27.1) at baseline. Median number of injected BMNCs was 2.20 x 108 (1.40-3.50 x 108). Change in LVEF did not differ significantly between treatment groups: trimmed mean ΔEF= 3.0 (1.3 to 4.8) for BMNC and 2.5 (0.6 to 4.5) for placebo (p=0.519) at 6 months; ΔEF= 3.5 (1.5 to 5.5) for BMNC and ΔEF= 3.7 (1.5 to 6.0) for placebo (p=0.850) at 12 months. Left ventricular systolic and diastolic volumes, NYHA class, Minnesota life quality questionnaire, BNP concentrations, and 6-min walking test did also not differ between groups. Conclusions —Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with CCC. Clinical Trial Registration Information —ClinicalTrials.gov; Identifier: [NCT00349271][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00349271&atom=%2Fcirculationaha%2Fearly%2F2012%2F04%2F19%2FCIRCULATIONAHA.111.067785.atomBackground— Previous studies suggested that transplantation of autologous bone marrow–derived mononuclear cells (BMNCs) improves heart function in chronic chagasic cardiomyopathy. We report the results of the first randomized trial of BMNC therapy in chronic chagasic cardiomyopathy. Methods and Results— Patients 18 to 75 years of age with chronic chagasic cardiomyopathy, New York Heart Association class II to IV heart failure, left ventricular ejection fraction (LVEF) <35, and optimized therapy were randomized to intracoronary injection of autologous BMNCs or placebo. The primary end point was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5. Between July 2005 and October 2009, 234 patients were enrolled. Two patients abandoned the study and 49 were excluded because of protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had a trimmed mean age of 52.4 years (range, 50.8–54.0 years) and LVEF of 26.1 (range, 25.1–27.1) at baseline. Median number of injected BMNCs was 2.20×108 (range, 1.40–3.50×108). Change in LVEF did not differ significantly between treatment groups: trimmed mean change in LVEF at 6 months, 3.0 (1.3–4.8) for BMNCs and 2.5 (0.6–4.5) for placebo (P=0.519); change in LVEF at 12 months, 3.5 (1.5–5.5) for BMNCs and 3.7 (1.5–6.0) for placebo (P=0.850). Left ventricular systolic and diastolic volumes, New York Heart Association functional class, Minnesota quality-of-life questionnaire, brain natriuretic peptide concentrations, and 6-minute walking test did also not differ between groups. Conclusion— Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with chronic chagasic cardiomyopathy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00349271.

Cardiac Magnetic Resonance-Verified Myocardial Fibrosis in Chagas Disease: Clinical Correlates and Risk Stratification

Background Chagas disease (CD) is an important cause of heart failure and mortality, mainly in Latin America. This study evaluated the morphological and functional characteristics of the heart as well the extent of myocardial fibrosis (MF) in patients with CD by cardiac magnetic resonance (CMR). The prognostic value of MF evaluated by myocardial-delayed enhancement (MDE) was compared with that via Rassi score. Methods This study assessed 39 patients divided into 2 groups: 28 asymptomatic patients as indeterminate form group (IND); and symptomatic patients as Chagas Heart Disease (CHD) group. All patients underwent CMR using the techniques of cine-MRI and MDE, and the amount of MF was compared with the Rassi score. Results Regarding the morphological and functional analysis, significant differences were observed between both groups (p < 0.001). Furthermore, there was a strong correlation between the extent of MF and the Rassi score (r = 0.76). Conclusions CMR is an important technique for evaluating patients with CD, stressing morphological and functional differences in all clinical presentations. The strong correlation with the Rassi score and the extent of MF detected by CMR emphasizes its role in the prognostic stratification of patients with CD.

Genetic Polymorphism at CCL5 Is Associated With Protection in Chagas’ Heart Disease: Antagonistic Participation of CCR1+ and CCR5+ Cells in Chronic Chagasic Cardiomyopathy

Chronic cardiomyopathy is the main clinical manifestation of Chagas disease (CD), a disease caused by Trypanosoma cruzi infection. A hallmark of chronic chagasic cardiomyopathy (CCC) is a fibrogenic inflammation mainly composed of CD8+ and CD4+ T cells and macrophages. CC-chemokine ligands and receptors have been proposed to drive cell migration toward the heart tissue of CD patients. Single nucleotide polymorphisms (SNPs) in CC-chemokine ligand and receptor genes may determine protein expression. Herein, we evaluated the association of SNPs in the CC-chemokines CCL2 (rs1024611) and CCL5 (rs2107538, rs2280788) and the CCL5/RANTES receptors CCR1 (rs3181077, rs1491961, rs3136672) and CCR5 (rs1799987) with risk and progression toward CCC. We performed a cross-sectional association study of 406 seropositive patients from endemic areas for CD in the State of Pernambuco, Northeast Brazil. The patients were classified as non-cardiopathic (A, n = 110) or cardiopathic (mild, B1, n = 163; severe, C, n = 133). Serum levels of CCL5 and CCL2/MCP-1 were elevated in CD patients but were neither associated with risk/severity of CCC nor with SNP genotypes. After logistic regression analysis with adjustment for the covariates gender and ethnicity, CCL5 −403 (rs2107538) CT heterozygotes (OR = 0.5, P-value = 0.04) and T carriers (OR = 0.5, P-value = 0.01) were associated with protection against CCC. To gain insight into the participation of the CCL5–CCR5/CCR1 axis in CCC, mice were infected with the Colombian T. cruzi strain. Increased CCL5 concentrations were detected in cardiac tissue. In spleen, frequencies of CCR1+ CD8+ T cells and CD14+ macrophages were decreased, while frequencies of CCR5+ cells were increased. Importantly, CCR1+CD14+ macrophages were mainly IL-10+, while CCR5+ cells were mostly TNF+. CCR5-deficient infected mice presented reduced TNF concentrations and injury in heart tissue. Selective blockade of CCR1 (Met-RANTES therapy) in infected Ccr5−/− mice supported a protective role for CCR1 in CCC. Furthermore, parasite antigen stimulation of CD patient blood cells increased the frequency of CCR1+CD8+ T cells and CCL5 production. Collectively, our data support that a genetic variant of CCL5 and CCR1+ cells confer protection against Chagas heart disease, identifying the CCL5-CCR1 axis as a target for immunostimulation.

Cell Therapy in Chagas Cardiomyopathy (Chagas Arm of the Multicenter Randomized Trial of Cell Therapy in Cardiopathies Study)Clinical Perspective

Background —Previous studies suggested that transplantation of autologous bone marrow derived mononuclear cells (BMNC) improves heart function in chronic chagasic cardiomyopathy (CCC). We report the results of the first randomized trial of BMNC therapy in CCC. Methods and Results —Patients aged 18-75 years with CCC, NYHA class III or IV, LVEF less than 35%, and optimized therapy were randomized to intracoronary injection of autologous BMNC or placebo. Primary endpoint was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5%. Between July 2005 and October 2009 234 patients were enrolled. Two abandoned the study and 49 were excluded due to protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had trimmed mean age of 52.4 years (50.8 to 54.0) and LVEF of 26.1% (25.1 to 27.1) at baseline. Median number of injected BMNCs was 2.20 x 108 (1.40-3.50 x 108). Change in LVEF did not differ significantly between treatment groups: trimmed mean ΔEF= 3.0 (1.3 to 4.8) for BMNC and 2.5 (0.6 to 4.5) for placebo (p=0.519) at 6 months; ΔEF= 3.5 (1.5 to 5.5) for BMNC and ΔEF= 3.7 (1.5 to 6.0) for placebo (p=0.850) at 12 months. Left ventricular systolic and diastolic volumes, NYHA class, Minnesota life quality questionnaire, BNP concentrations, and 6-min walking test did also not differ between groups. Conclusions —Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with CCC. Clinical Trial Registration Information —ClinicalTrials.gov; Identifier: [NCT00349271][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00349271&atom=%2Fcirculationaha%2Fearly%2F2012%2F04%2F19%2FCIRCULATIONAHA.111.067785.atomBackground— Previous studies suggested that transplantation of autologous bone marrow–derived mononuclear cells (BMNCs) improves heart function in chronic chagasic cardiomyopathy. We report the results of the first randomized trial of BMNC therapy in chronic chagasic cardiomyopathy. Methods and Results— Patients 18 to 75 years of age with chronic chagasic cardiomyopathy, New York Heart Association class II to IV heart failure, left ventricular ejection fraction (LVEF) <35, and optimized therapy were randomized to intracoronary injection of autologous BMNCs or placebo. The primary end point was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5. Between July 2005 and October 2009, 234 patients were enrolled. Two patients abandoned the study and 49 were excluded because of protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had a trimmed mean age of 52.4 years (range, 50.8–54.0 years) and LVEF of 26.1 (range, 25.1–27.1) at baseline. Median number of injected BMNCs was 2.20×108 (range, 1.40–3.50×108). Change in LVEF did not differ significantly between treatment groups: trimmed mean change in LVEF at 6 months, 3.0 (1.3–4.8) for BMNCs and 2.5 (0.6–4.5) for placebo (P=0.519); change in LVEF at 12 months, 3.5 (1.5–5.5) for BMNCs and 3.7 (1.5–6.0) for placebo (P=0.850). Left ventricular systolic and diastolic volumes, New York Heart Association functional class, Minnesota quality-of-life questionnaire, brain natriuretic peptide concentrations, and 6-minute walking test did also not differ between groups. Conclusion— Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with chronic chagasic cardiomyopathy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00349271.

Cell Therapy in Chagas Cardiomyopathy (Chagas Arm of the Multicenter Randomized Trial of Cell Therapy in Cardiopathies Study)

Background —Previous studies suggested that transplantation of autologous bone marrow derived mononuclear cells (BMNC) improves heart function in chronic chagasic cardiomyopathy (CCC). We report the results of the first randomized trial of BMNC therapy in CCC. Methods and Results —Patients aged 18-75 years with CCC, NYHA class III or IV, LVEF less than 35%, and optimized therapy were randomized to intracoronary injection of autologous BMNC or placebo. Primary endpoint was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5%. Between July 2005 and October 2009 234 patients were enrolled. Two abandoned the study and 49 were excluded due to protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had trimmed mean age of 52.4 years (50.8 to 54.0) and LVEF of 26.1% (25.1 to 27.1) at baseline. Median number of injected BMNCs was 2.20 x 108 (1.40-3.50 x 108). Change in LVEF did not differ significantly between treatment groups: trimmed mean ΔEF= 3.0 (1.3 to 4.8) for BMNC and 2.5 (0.6 to 4.5) for placebo (p=0.519) at 6 months; ΔEF= 3.5 (1.5 to 5.5) for BMNC and ΔEF= 3.7 (1.5 to 6.0) for placebo (p=0.850) at 12 months. Left ventricular systolic and diastolic volumes, NYHA class, Minnesota life quality questionnaire, BNP concentrations, and 6-min walking test did also not differ between groups. Conclusions —Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with CCC. Clinical Trial Registration Information —ClinicalTrials.gov; Identifier: [NCT00349271][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00349271&atom=%2Fcirculationaha%2Fearly%2F2012%2F04%2F19%2FCIRCULATIONAHA.111.067785.atomBackground— Previous studies suggested that transplantation of autologous bone marrow–derived mononuclear cells (BMNCs) improves heart function in chronic chagasic cardiomyopathy. We report the results of the first randomized trial of BMNC therapy in chronic chagasic cardiomyopathy. Methods and Results— Patients 18 to 75 years of age with chronic chagasic cardiomyopathy, New York Heart Association class II to IV heart failure, left ventricular ejection fraction (LVEF) <35, and optimized therapy were randomized to intracoronary injection of autologous BMNCs or placebo. The primary end point was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5. Between July 2005 and October 2009, 234 patients were enrolled. Two patients abandoned the study and 49 were excluded because of protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had a trimmed mean age of 52.4 years (range, 50.8–54.0 years) and LVEF of 26.1 (range, 25.1–27.1) at baseline. Median number of injected BMNCs was 2.20×108 (range, 1.40–3.50×108). Change in LVEF did not differ significantly between treatment groups: trimmed mean change in LVEF at 6 months, 3.0 (1.3–4.8) for BMNCs and 2.5 (0.6–4.5) for placebo (P=0.519); change in LVEF at 12 months, 3.5 (1.5–5.5) for BMNCs and 3.7 (1.5–6.0) for placebo (P=0.850). Left ventricular systolic and diastolic volumes, New York Heart Association functional class, Minnesota quality-of-life questionnaire, brain natriuretic peptide concentrations, and 6-minute walking test did also not differ between groups. Conclusion— Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with chronic chagasic cardiomyopathy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00349271.