CHARLES MADY
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina - Líder
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conferenceObject Echocardiographic findings of Trypanosoma cruzi seropositive blood donors(2017) SALEMI, V. M. C.; OLIVEIRA, C. D. L.; RIBEIRO, A. L.; MENEZES, M. M.; ANTUNES, A. P.; FERREIRA-FILHO, J. C.; SACHDEV, V.; FERNANDES, F.; NASTARI, L.; IANNI, B. M.; MADY, C.; CARNEIRO-PROIETTI, A. B.; KEATING, S. M.; BUSCH, M. P.; SABINO, E. G.- Detection of Early Diffuse Myocardial Fibrosis and Inflammation in Chagas Cardiomyopathy with T1 Mapping and Extracellular Volume(2023) MELO, Rodrigo J. L.; ASSUNCAO, Antonildes N.; MORAIS, Thamara C.; NOMURA, Cesar H.; SCANAVACCA, Mauricio I.; MARTINELLI-FILHO, Martino; RAMIRES, Felix J. A.; FERNANDES, Fabio; IANNI, Barbara M.; MADY, Charles; ROCHITTE, Carlos E.Purpose: To evaluate myocardial T1 mapping and extracellular volume (ECV) parameters in different stages of Chagas cardiomyopathy and determine whether they are predictive of disease severity and prognosis.Materials and Methods: Prospectively enrolled participants (July 2013 to September 2016) underwent cine and late gadolinium enhancement (LGE) cardiac MRI and T1 mapping with a precontrast (native) or postcontrast modified Look-Locker sequence. The native T1 and ECV values were measured among subgroups that were based on disease severity (indeterminate, Chagas cardiomyopathy with preserved ejection fraction [CCpEF], Chagas cardiomyopathy with midrange ejection fraction [CCmrEF], and Chagas cardiomyopathy with reduced ejection fraction [CCrEF]). Cox proportional hazards regression and the Akaike information criterion were used to determine predictors of major cardiovascular events (cardioverter defibrillator implant, heart transplant, or death).Results: In 107 participants (90 participants with Chagas disease [mean age & PLUSMN; SD, 55 years & PLUSMN; 11; 49 men] and 17 age-and sex matched control participants), the left ventricular (LV) ejection fraction and the extent of focal and diffuse or interstitial fibrosis were correlated with disease severity. Participants with CCmrEF and participants with CCrEF showed significantly higher global native T1 and ECV values than participants in the indeterminate, CCpEF, and control groups (T1: 1072 msec & PLUSMN; 34 and 1073 msec & PLUSMN; 63 vs 1010 msec & PLUSMN; 41, 1005 msec & PLUSMN; 69, and 999 msec & PLUSMN; 46; ECV: 35.5% & PLUSMN; 3.6 and 35.0% & PLUSMN; 5.4 vs 25.3% & PLUSMN; 3.5, 28.2% & PLUSMN; 4.9, and 25.2% & PLUSMN; 2.2; both P < .001). Remote (LGE-negative areas) native T1 and ECV values were also higher (T1: 1056 msec & PLUSMN; 32 and 1071 msec & PLUSMN; 55 vs 1008 msec & PLUSMN; 41, 989 msec & PLUSMN; 96, and 999 msec & PLUSMN; 46; ECV: 30.2% & PLUSMN; 4.7 and 30.8% & PLUSMN; 7.4 vs 25.1% & PLUSMN; 3.5, 25.1% & PLUSMN; 3.7, and 25.0% & PLUSMN; 2.2; both P < .001). Abnormal remote ECV values (>30%) occurred in 12% of participants in the indeterminate group, which increased with disease severity. Nineteen combined outcomes were observed (median follow-up time: 43 months), and a remote native T1 value greater than 1100 msec was independently predictive of combined outcomes (hazard ratio, 12 [95% CI: 4.1, 34.2]; P < .001).Conclusion: Myocardial native T1 and ECV values were correlated with Chagas disease severity and may serve as markers of myocardial involvement in Chagas cardiomyopathy that precede LGE and LV dysfunction.
conferenceObject Whole exome sequencing of Chagas disease cardiomyopathy families reveals accumulation of rare variants in mitochondrial and inflammation-associated genes(2019) CUNHA-NETO, E.; MARQUET, S.; FRADE, A. Farage; FERREIRA, A. Mota; OUARHACHE, M.; IANNI, B.; FERREIRA, L. Rodrigues Pinto; RIGAUD, V. Oliveira-Carvalho; ALMEIDA, R. Ribeiro; CANDIDO, D.; TORRES, M.; GALLARDO, F.; FERNANDES, R.; MADY, C.; BUCK, P.; CARDOSO, C.; SANTOS-JUNIOR, O. R.; OLIVEIRA, L. C.; OLIVEIRA, C. D. L.; NUNES, M. do Carmo; ABEL, L.; KALIL, J.; RIBEIRO, A. L. P.; SABINO, E. C.; CHEVILLARD, C.- Chagas' heart disease: gender differences in myocardial damage assessed by cardiovascular magnetic resonance(2016) ASSUNCAO JR., Antonildes N.; JEROSCH-HEROLD, Michael; MELO, Rodrigo L.; MAURICIO, Alejandra V.; ROCHA, Liliane; TORREAO, Jorge A.; FERNANDES, Fabio; IANNI, Barbara M.; MADY, Charles; KALIL-FILHO, Roberto; ROCHITTE, Carlos E.Background: Since a male-related higher cardiovascular morbidity and mortality in patients with Chagas' heart disease has been reported, we aimed to investigate gender differences in myocardial damage assessed by cardiovascular magnetic resonance (CMR). Methods and results: Retrospectively, 62 seropositive Chagas' heart disease patients referred to CMR (1.5 T) and with low probability of having significant coronary artery disease were included in this analysis. Amongst both sexes, there was a strong negative correlation between LV ejection fraction and myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males showing significantly greater myocardial fibrosis (P = 0.002) and lower LV ejection fraction (P < 0.001) than females. After adjustment for potential confounders, gender remained associated with myocardial dysfunction, and 53% of the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also, the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P < 0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P = 0.003). Conclusions: We observed gender-related differences in myocardial damage assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis and myocardial dysfunction are associated to cardiovascular outcomes, our findings might help to understand the poorer prognosis observed in males in Chagas' disease.
bookPart Afecções Pericárdicas Agudas: Pericardite Aguda e Tamponamento Pericárdico(2013) FERNANDES, Fábio; IANNI, Barbara Maria; MADY, Charles- Rare association of endomyocardial fibrosis and Chagas heart disease(2017) HOTTA, Viviane Tiemi; IANNI, Barbara Maria; ASSUNCAO JR., Antonildes Nascimento; PARGA, Jose Rodrigues; MADY, Charles
- IMPACT OF AIR POLLUTION ON MYOCARDIAL REMODELING IN CHAGA'S DISEASE(2019) FONSECA, Keila; PESSOA, Fernanda; MADY, Charles; HOTTA, Viviane; RIBEIRO, Orlando N.; FERNANDES, Fabio; IANNI, Barbara; SALDIVA, Paulo; RAMIRES, Felix
- Air Pollution's Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy(2022) FONSECA, Keila Cardoso Barbosa; PESSOA, Fernanda Gallinaro; RIBEIRO, Orlando do Nascimento; HOTTA, Viviane Tiemi; IANNI, Barbara Maria; FERNANDES, Fabio; RIVERO, Dolores Helena Rodriguez Ferreira; SALDIVA, Paulo Hilario Nascimento; MADY, Charles; RAMIRES, Felix Jose AlvarezBackgroundChagas disease is characterized by intense myocardial fibrosis stimulated by the exacerbated production of inflammatory cytokines, oxidative stress, and apoptosis. Air pollution is a serious public health problem and also follows this same path. Therefore, air pollution might amplify the inflammatory response of Chagas disease and increase myocardial fibrosis. MethodsWe studied groups of Trypanosoma cruzi infected Sirius hamsters (Chagas=CH and Chagas exposed to pollution=CH+P) and 2 control groups (control healthy animals=CT and control exposed to pollution=CT+P). We evaluated acute phase (60 days post infection) and chronic phase (10 months). Echocardiograms were performed to assess left ventricular systolic and diastolic diameter, in addition to ejection fraction. Interstitial collagen was measured by morphometry in picrosirius red staining tissue. The evaluation of inflammation was performed by gene and protein expression of cytokines IL10, IFN-gamma, and TNF; oxidative stress was quantified by gene expression of NOX1, MnSOD, and iNOS and by analysis of reactive oxygen species; and apoptosis was performed by gene expression of BCL2 and Capsase3, in addition to TUNEL analysis. ResultsChagas groups had increased collagen deposition mainly in the acute phase, but air pollution did not increase this deposition. Also, Chagas groups had lower ejection fraction in the acute phase (p = 0.002) and again air pollution did not worsen ventricular function or dilation. The analysis of the inflammation and oxidative stress pathways were also not amplified by air pollution. Apoptosis analysis showed increased expression of BCL2 and Caspase3 genes in chagasic groups in the acute phase, with a marginal p of 0.054 in BCL2 expression among infected groups, and TUNEL technique showed amplified of apoptotic cells by pollution among infected groups. ConclusionsA possible modulation of the apoptotic pathway was observed, inferring interference from air pollution in this pathway. However, it was not enough to promote a greater collagen deposition, or worsening ventricular function or dilation caused by air pollution in this model of Chagas cardiomyopathy.
conferenceObject Lack of Effect of Simvastatin on Structural Remodeling in Animal Model of Chagas Cardiomyopathy(2012) IANNI, Barbara M.; RAMIRES, Felix J. A.; SALEMI, Vera M. C.; FERNANDES, Fabio; OLIVEIRA, Adriana M.; PESSOA, Fernanda G.; FONSECA, Keila C. B.; ARTEAGA, Edmundo; NASTARI, Luciano; MADY, CharlesPurpose: Chagas cardiomyopathy(CM) is characterized by a large amount of fibrosis and inflamation. As simvastatin (simva) has anti-inflamatory effects, we hypothetized that it could be an important drug in the treatment of patients with CM. The purpose was to evaluate simva in the myocardium remodeling and inflammation in na animal model of CM. Methods: 123 hamsters were divided: C-controls(25), CSimva-controls with simva 10mg/Kg/day(25), Simva1-infected treated from beginning with the same dose of simva(25), Simva2-infected treated after 4 months(24); Infect-untreated(24). Follow-up of 10 months. Interstitial collagen volume fraction (ICVF) RV and LV measured using videomorphometry and picrosirius red stained heart. Metalloproteinase9 (MMP9) was obtained by zymography. Gene expression of TNFalpha, IFNgamma, IL10 by real time PCR and ΔCt. Survival by Kaplan-Meier and log rank. Comparison between groups by Kruskal-Wallis; p≤0.05. Results: Infected animals Simva1=189±133 days Simva2=150±124; Infect=138±123) lived less than controls (C=257±80; CSimva=283±58)(p≤0.05) with no difference among infected. ICVF-RV(%) was greater in infected groups (Simva1=3.88±1.14, Simva2=2.22±0.64; Infect=4.38±0.83) than in controls C=1.12±0.31; CSimva=2.18±0.73)(p≤0.05)with no difference among infected groups. ICVF-LV(%) was greater in infected animals (Simva1=1.83±1.01, Simva2=1.52±0.93; Infect=3.01±0.66) than in controls (C=0.68±0.31; CSimva=0.81±0.28)(p≤0.05) with no difference among infected. MMP9 was higher in infected groups (Simva1=2394±2441, Simva2=5673±4091; Infect=2392±2042) compared to controls (C=954±2332; CSimva=454±1123)(p≤0.05) with no difference among infected. TNFalpha did not have difference among infected groups (Simva1=5.33±3.66, Simva2=4.44±2.17; Infect=6.13±3.24). IFNgamma in infected groups (Simva1=5.47±3.56, Simva2=4.46±2.08; Infect=4.21±2.09) was higher than in controls (C=8.50±2.59; CSimva=6.84±2.53)(p≤0.05) with no difference among infected. IL10 in infected animals (Simva1=9.07±4.62, Simva2=7.76±4.77; Infect=8.11±4.48) did not have difference and the values were greater than controls (C=14.11±4.40; CSimva=12.55±3.90)(p≤0.05). Conclusions: Simva did not attenuate deposition of interstitial collagen, did not change dynamics of collagen degradation, did not decrease inflammation, and did not reduce mortality.- SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease-2023(2023) MARIN-NETO, Jose Antonio; JR, Anis Rassi; OLIVEIRA, Glaucia Maria Moraes; CORREIA, Luis Claudio Lemos; RAMOS JUNIOR, Alberto Novaes; LUQUETTI, Alejandro Ostermayer; HASSLOCHER-MORENA, Alejandro Marcel; SOUSA, Andrea Silvestre de; PAOLA, Angelo Amato Vincenzo de; SOUSA, Antonio Carlos Sobral; RIBEIRO, Antonio Luiz Pinho; CORREIA FILHO, Dalmo; SOUZA, Dilma do Socorro Moraes de; CUNHA-NETO, Edecio; RAMIRES, Felix Jose Alvarez; BACAL, Fernando; NUNES, Maria do Carmo Pereira; MARTINELLI FILHO, Martino; SCANAVACCA, Maurici Ibrahim; SARAIVA, Roberto Magalhaes; OLIVEIRA JUNIOR, Wilson Alves de; LORGA-FILHO, Adalberto Menezes; GUIMARAES, Adriana de Jesus Benevides de Almeida; BRAGA, Adriana Lopes Latado; OLIVEIRA, Adriana Sarmento de; SARABANDA, Alvaro Valentim Lima; PINTO, Ana Yece das Neves; CARMO, Andre Assis Lopes do; SCHMIDT, Andre; COSTA, Andrea Rodrigues da; IANNI, Barbara Maria; MARKMAN FILHO, Brivaldo; ROCHITT, Carlos Eduardo; MACEDO, Carolina The; MADY, Charles; CHEVILLARD, Christophe; VIRGENS, Claudio Marcelo Bittencourt das; CASTRO, Cleudson Nery de; BRITTO, Constanca Felicia De Paoli de Carvalho; PISANI, Cristiano; RASSI, Daniel do Carmo; SOBRAL FILHO, Dario Celestino; ALMEIDA, Dirceu Rodrigues de; BOCCHI, Edimar Alcides; MESQUITA, Evandro Tinoco; MENDES, Fernanda de Souza Nogueira Sardinha; GONDIM, Francisca Tatiana Pereira; SILVA, Gilberto Marcelo Sperandio da; PEIXOTO, Giselle de Lima; LIMA, Gustavo Glotz de; VELOSO, Henrique Horta; MOREIRA, Henrique Turin; LOPES, Hugo Bellotti; PINTO, Ibraim Masciarelli Francisco; FERREIRA, Joao Marcos Bemfica Barbosa; NUNES, Joao Paulo Silva; BARRETO-FILHO, Jose Augusto Soares; SARAIVA, Jose Francisco Kerr; LANNES-VIEIRA, Joseli; OLIVEIRA, Joselina Luzia Menezes; ARMAGANIJAN, Luciana Vidal; MARTINS, Luiz Claudio; SANGENIS, Luiz Henrique Conde; BARBOSA, Marco Paulo Tomaz; ALMEIDA-SANTOS, Marcos Antonio; SIMOES, Marcos Vinicius; YASUDA, Maria Aparecida Shikanai; MOREIRA, Maria da Consolacao Vieira; HIGUCHI, Maria de Lourdes; MONTEIRO, Maria Rita de Cassia Costa; MEDIANO, Mauro Felippe Felix; LIMA, Mayara Maia; OLIVEIRA, Maykon Tavares de; ROMANO, Minna Moreira Dias; ARAUJO, Nadjar Nitz Silva Lociks de; MEDEIROS, Paulo de Tarso Jorge; ALVES, Renato Vieira; TEIXEIRA, Ricardo Alkmim; PEDROSA, Roberto Coury; ARAS JUNIOR, Roque; TORRES, Rosalia Morais; POVOA, Rui Manoel dos Santos; RASSI, Sergio Gabriel; ALVES, Silvia Marinho Martins; TAVARES, Suelene Brito do Nascimento; PALMEIRA, Swamy Lima; SILVA JUNIOR, Telemaco Luiz da; RODRIGUES, Thiago da Rocha; MADRINI JUNIOR, Vagner; BRANT, Veruska Maia da Costa; DUTRA, Walderez Ornelas; DIAS, Joao Carlos Pinto