ANTONIO AUGUSTO BARBOSA LOPES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Circulating Levels of MIF, GRO alpha And RANTES Chemokines and Interleukin 17E Correlate With Severity of Pulmonary Hypertension in Young Pediatric Patients With Congenital Heart Disease(2015) ZORZANELLI, Leina; MAEDA, Nair Y.; CLEVE, Mariana M.; THOMAZ, Ana M.; RABINOVITCH, Marlene; LOPES, Antonio A.- Parameters associated with outcome in pediatric patients with congenital heart disease and pulmonary hypertension subjected to combined vasodilator and surgical treatments(2019) THOMAZ, Ana Maria; KAJITA, Luiz J.; AIELLO, Vera D.; ZORZANELLI, Leina; GALAS, Filomena Regina B. G.; MACHADO, Cleide G.; BARBERO-MARCIAL, Miguel; JATENE, Marcelo B.; RABINOVITCH, Marlene; LOPES, Antonio AugustoManagement of pediatric pulmonary hypertension associated with congenital heart disease (PHT-CHD) is challenging. Some patients have persistently elevated pulmonary artery pressure (PAP) after cardiac surgery, an undesired condition that is difficult to predict. We investigated the value of clinical, hemodynamic, and histopathological data in predicting the outcome in a prospective cohort. Patients with PHT-CHD received sildenafil orally pre- and postoperatively for six months and then were subjected to a catheter study. Thirty-three patients were enrolled (age range = 4.6-37.0 months). Pulmonary vascular resistance (PVR) was 4.9 (range = 3.9-7.2) Wood units x m(2) (median with IQR). Twenty-two patients had a >= 20% decrease in PVR and pulmonary-to-systemic vascular resistance ratio (PVR/SVR) in response to inhaled nitric oxide (NO). The response was directly related to the degree of medial hypertrophy of pulmonary arterioles (P < 0.05) (morphometric analysis, intraoperative lung biopsy). Subsequently, five of the non-responders had a >= 30% increase in pulmonary blood flow in response to sildenafil (3.0 [2.0-4.0] mg/kg/day). Six months after surgery, PAP and PVR were significantly lower (P < 0.001 vs. baseline), even in seven patients with Heath-Edwards grade III/IV pulmonary vascular lesions (P = 0.018), but still abnormal in 12 individuals (>25 mmHg and >3.0 U x m(2), respectively). A preoperative PVR/SVR of >= 24% during NO inhalation and a wall thickness of arteries accompanying respiratory bronchioli of >= 4.7 (Z score) were identified, respectively, as risk and protection factors for abnormal postoperative hemodynamics (hazard ratio [95% CI] = 1.09 [1.01-1.18], P = 0.036; and 0.69 [0.49-0.98], P = 0.040, respectively). Thus, in PHT-CHD patients receiving oral sildenafil pre- and post-surgical repair of cardiac lesions, mid-term postoperative outcome is predictable to some extent.
- Relation of Cytokine Profile to Clinical and Hemodynamic Features in Young Patients With Congenital Heart Disease and Pulmonary Hypertension(2017) ZORZANELLI, Leina; MAEDA, Nair; CLAVE, Mariana; THOMAZ, Ana; GALAS, Filomena; RABINOVITCH, Marlene; LOPES, AntonioIn congenital heart disease, severity of pulmonary hypertension and operability is defined by noninvasive parameters (clinical history, physical examination, and echocardiography) and sometimes, cardiac catheterization. We investigated how circulating levels of inflammatory mediators correlate with such parameters in a young pediatric population (age, 2.0 months to 3.1 years) and the effects of preoperative pulmonary vasodilator therapy with sildenafil. Cytokines were analyzed in serum using chemiluminescence signals. In the whole patient group (n = 47), interleukin 17E, a Th2 immune response mediator increased with increasing age, considered as a parameter of disease severity (R-2 = 0.24, p <0.001), whereas the angiogenic chemokine growth-regulated oncogene alpha decreased (R-2 = 0.21, p = 0.001). Macrophage migration inhibitory factor chemokine was greater in subjects with elevated pulmonary vascular resistance (n = 16, p = 0.022), whereas regulated on activation, normal T cell expressed and secreted chemokine was greater in subjects with pulmonary congestion due to increased pulmonary blood flow (n = 31, p = 0.037). The observations were the same for the specific subpopulation of patients with Down syndrome (p = 0.009 and p = 0.012 for migration inhibitory factor and regulated on activation, normal T cell expressed and secreted in the respective subgroups). Sildenafil administration to patients with elevated pulmonary vascular resistance resulted in improvement of pulmonary blood flow (p = 0.012) and systemic oxygen saturation (p = 0.010), with a decrease in serum interleukin 6 (p = 0.027) and soluble ICAM-1 (p = 0.011). In conclusion, levels of circulating inflammatory molecules seem to correlate with disease severity in this population, with potential pathophysiological and therapeutic implications.
conferenceObject Circulating Levels of RANTES Chemokine Correlate With Pulmonary Hemodynamic Patterns in Pediatric Patients With Congenital Cardiac Communications(2018) SOUZA, Maria F.; MAEDA, Nair Y.; CASTRO, Claudia R.; ZORZANELLI, Leina; CLAVE, Mariana M.; LOPES, Antonio A.- Heart Neoplasms in Children: Retrospective Analysis(2013) PENHA, Juliano Gomes; ZORZANELLI, Leina; BARBOSA-LOPES, Antonio Augusto; AIELLO, Vera Demarchi; CARVALHO, Vitor Oliveira; CANEO, Luiz Fernando; RISO, Arlindo de Almeida; TANAMATI, Carla; ATIK, Edimar; JATENE, Marcelo BiscegliBackground: The advancement of noninvasive imaging methods has resulted in the increase in diagnosis of heart neoplasms. However, the literature has few studies involving primary cardiac neoplasms in children. Objective: To retrospectively review cases of primary heart neoplasms in children, considering the initial clinical manifestations, diagnostic tests used, surgical indication, histopathological types and immediate postoperative course. Methods: The retrospective study was based on the assessment of medical records from 1983 to 2011. Only cases that were referred for surgical treatment during that period were included. Age at admission, prenatal diagnosis, family history, initial symptoms and the results of performed tests were assessed. Moreover, the date and indication of the surgery, intraoperative findings, the result of the histopathological analysis, as well as the immediate postoperative complications were recorded. Results: Of the 18 patients studied, the most frequent clinical manifestations were dyspnea and heart murmur (7 and 6 patients, respectively); the most often used adjunct diagnostic method was echocardiography (18 patients); cavitary obstruction or ventricular inflow or outflow tract obstruction was the main indication for surgery (12 cases); the most common histological profile was rhabdomyoma (7 patients) and most patients showed good clinical outcome. Conclusion: In this study, imaging diagnosis was basically attained through echocardiography, with good correlation with intraoperative findings. Histopathological findings were consistent with the literature, with rhabdomyoma being the most common neoplasm in children. The evolution after surgical treatment was favorable in most cases. (Arq Bras Cardiol. 2013; 100(2): 120-126)
- Repair of congenital heart disease with associated pulmonary hypertension in children: what are the minimal investigative procedures? Consensus statement from the Congenital Heart Disease and Pediatric Task Forces, Pulmonary Vascular Research Institute (PVRI)(2014) LOPES, Antonio Augusto; BARST, Robyn J.; HAWORTH, Sheila Glennis; RABINOVITCH, Marlene; DABBAGH, Maha Al; CERRO, Maria Jesus del; IVY, Dunbar; KASHOUR, Tarek; KUMAR, Krishna; HARIKRISHNAN, S.; D'ALTO, Michele; THOMAZ, Ana Maria; ZORZANELLI, Leina; AIELLO, Vera D.; MOCUMBI, Ana Olga; SANTANA, Maria Virginia T.; GALAL, Ahmed Nasser; BANJAR, Hanaa; TAMIMI, Omar; HEATH, Alexandra; FLORES, Patricia C.; DIAZ, Gabriel; SANDOVAL, Julio; KOTHARI, Shyam; MOLEDINA, Shahin; GONCALVES, Rilvani C.; BARRETO, Alessandra C.; BINOTTO, Maria Angelica; MAIA, Margarida; HABSHAN, Fahad Al; ADATIA, IanStandardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e. g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation.
- Macrophage migration inhibitory factor and chemokine RANTES in young pediatric patients with congenital cardiac communications: Relation to hemodynamic parameters and the presence of Down syndrome(2020) SOUZA, Maria Francilene S.; CARVALHO, Eloisa S.; MAEDA, Nair Y.; THOMAZ, Ana M.; ZORZANELLI, Leina; CASTRO, Claudia R.; PEREIRA, Juliana; LOPES, Antonio AugustoInflammation and immunity are central in the pathobiology of pulmonary vascular disorders. Preliminary headway has been made in understanding the relationships between inflammatory proteins and clinical parameters in pediatric congenital heart disease. In this study, we analyzed serum levels of macrophage migration inhibitory factor (MIF) and regulated on activation normal T cell expressed and secreted chemokine (RANTES) in 87 patients with unrestrictive congenital cardiac communications and signs of pulmonary hypertension (age 2-36 months) and 50 pediatric controls. They were investigated in relation to clinical and hemodynamic parameters and the presence of Down syndrome. Hemodynamics was assessed by transthoracic Doppler echocardiography and cardiac catheterization. Chemokines were analyzed in serum using a chemiluminescence assay. The highest MIF levels were observed in very young subjects with heightened pulmonary vascular resistance but who presented a positive response to vasodilator challenge with inhaled nitric oxide. In contrast, RANTES levels were higher in patients with pulmonary overcirculation and congestion, correlating nonlinearly with pulmonary blood flow. Levels of both chemokines were higher in subjects with Down syndrome than in nonsyndromic individuals, but the difference was observed only in patients, not in the control group. In patients with Down syndrome, there was a direct relationship between preoperative serum MIF and the level of pulmonary artery pressure observed 6 months after surgical repair of cardiac anomalies. Thus, it was interesting to observe that MIF, which is key in the innate immune response and chemokine RANTES, which is highly expressed in respiratory viral infections were related to clinical and hemodynamic abnormalities associated with pediatric congenital heart disease.
- Serum Cytokines in Young Pediatric Patients with Congenital Cardiac Shunts and Altered Pulmonary Hemodynamics(2016) ZORZANELLI, Leina; MAEDA, Nair Yukie; CLAVE, Mariana Meira; AIELLO, Vera Demarchi; RABINOVITCH, Marlene; LOPES, Antonio AugustoBackground and Objective. Inflammation is central in the pathogenesis of pulmonary hypertension. We investigated how serum cytokines correlate with clinical features, hemodynamics, and lung histology in young patients with pulmonary hypertension associated with congenital cardiac shunts. Design. Prospective, observational study. Methods and Results. Patients (n = 44) were aged 2.6 to 37.6 months. Group I patients (n = 31) were characterized by pulmonary congestion and higher pulmonary blood flow compared to group II (p = 0.022), with no need for preoperative cardiac catheterization. Group II patients (n = 13) had no congestive features. At catheterization, they had elevated pulmonary vascular resistance (5.7 [4.4-7.4] Wood units.m(2), geometric mean with 95% CI). Cytokines were measured by chemiluminescence. Macrophage migration inhibitory factor (MIF) was found to be inversely related to pulmonary blood flow(r = -0.33,p = 0.026) and was higher in group II (high pulmonary vascular resistance) compared to group I (high pulmonary blood flow) (p = 0.017). In contrast, RANTES chemokine (regulated on activation, normal T cell expressed and secreted) was characteristically elevated in Group I (p = 0.022). Interleukin 16 was also negatively related to pulmonary blood flow (r(s) = -0.33, p = 0.029) and was higher in patients with obstructive vasculopathy at intraoperative lung biopsy (p = 0.021). Conclusion. Cytokines seem to be important and differentially regulated in subpopulations of young patients with cardiac shunts.
- Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension(2015) PENHA, Juliano Gomes; ZORZANELLI, Leina; BARBOSA-LOPES, Antonio Augusto; ATIK, Edimar; MIANA, Leonardo Augusto; TANAMATI, Carla; CANEO, Luiz Fernando; MIURA, Nana; AIELLO, Vera Demarchi; JATENE, Marcelo BiscegliBackground: Transposition of the great arteries (TGA) is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level. Objective: Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure. Method: Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included. Results: After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced. Conclusion: The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis.
conferenceObject Pulmonary Vascular Response to Inhaled Nitric Oxide is Related to the Mitochondrial Enzyme Carbamyl-Phosphate Synthetase I T1405N Polymorphism in Pediatric Patients With Congenital Cardiac Communications(2018) THOMAZ, Ana M.; KAJITA, Luiz J.; ZORZANELLI, Leina; SANTOS, Paulo C.; MIURA, Nana; LOPES, Antonio A.