ANTONIO AUGUSTO BARBOSA LOPES
Projetos de Pesquisa
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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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- Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study(2023) ABUD, Kelly C. O.; MACHADO, Clarisse M.; BOAS, Lucy S. Vilas S.; MAEDA, Nair Y.; CARVALHO, Eloisa S.; SOUZA, Maria Francilene S.; GAIOLLA, Paula V.; CASTRO, Claudia R. P.; PEREIRA, Juliana; RABINOVITCH, Marlene; LOPES, Antonio AugustoBackgroundPulmonary vascular abnormalities pose a risk for severe life-threatening hemodynamic disturbances following surgical repair of congenital cardiac communications (CCCs). In the distal lung, small airways and vessels share a common microenvironment, where biological crosstalks take place. Because respiratory cells infected by viruses express a number of molecules with potential impact on airway and vascular remodeling, we decided to test the hypothesis that CCC patients carrying viral genomes in the airways might be at a higher risk for pulmonary (and systemic) hemodynamic disturbances postoperatively.MethodsSixty patients were prospectively enrolled (age 11 [7-16] months, median with interquartile range). Preoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was 0.78 (0.63-0.88). The presence or absence of genetic material for respiratory viruses in nasopharyngeal and tracheal aspirates was investigated preoperatively in the absence of respiratory symptoms using real-time polymerase chain reaction (kit for detection of 19 pathogens). Post-cardiopulmonary bypass (CPB) inflammatory reaction was analyzed by measuring serum levels of 36 inflammatory proteins (immunoblotting) 4 h after its termination. Postoperative hemodynamics was assessed using continuous recording of PAP and SAP with calculation of PAP/SAP ratio.ResultsViral genomes were detected in nasopharynx and the trachea in 64% and 38% of patients, respectively. Rhinovirus was the most prevalent agent. The presence of viral genomes in the trachea was associated with an upward shift of postoperative PAP curve (p = 0.011) with a PAP/SAP of 0.44 (0.36-0.50) in patients who were positive versus 0.34 (0.30-0.45) in those who were negative (p = 0.008). The presence or absence of viral genomes in nasopharynx did not help predict postoperative hemodynamics. Postoperative PAP/SAP was positively correlated with post-CPB levels of interleukin-1 receptor antagonist (p = 0.026), macrophage migration inhibitory factor (p = 0.019) and monocyte chemoattractant protein-1 (p = 0.031), particularly in patients with virus-positive tracheal aspirates.ConclusionsPatients with CCCs carrying respiratory viral genomes in lower airways are at a higher risk for postoperative pulmonary hypertension, thus deserving special attention and care. Preoperative exposure to respiratory viruses and post-CPB inflammatory reaction seem to play a combined role in determining the postoperative behavior of the pulmonary circulation.
- 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.
- Acute vasoreactivity testing in pediatric idiopathic pulmonary arterial hypertension: an international survey on current practice(2019) CAICEDO, Lina; HOPPER, Rachel; AGUILAR, Humberto Garcia; IVY, Dunbar; HAAG, Dora; FINEMAN, Jeff; HUMPL, Tillman; AL-TAMIMI, Omar; FEINSTEIN, Jeff A.; BERGER, Rolf; ROSENZWEIG, Erika; KASHOUR, Tarek; DIAZ, Gabriel Fernando; MENDOZA, Alberto; KRISHNAN, Usha; BOBHATE, Prashant; HANDLER, Stephanie; LOPES, Antonio Augusto; RAHIT, Manoj Kumar; BARWARD, Parag; LERA, Carlos Labrandero de; ADATIA, Ian; MOLEDINA, Shahin; ABMAN, Steven; CERRO, Maria Jesus delThe aim of this study was to determine practice patterns and inter-institutional variability in how acute vasoreactivity testing (AVT) is performed and interpreted in pediatrics throughout the world. A survey was offered to physicians affiliated with the Pediatric & Congenital Heart Disease Taskforce of the Pulmonary Vascular Research Institute (PVRI), the Pediatric Pulmonary Hypertension Network (PPHNET), or the Spanish Registry for Pediatric Pulmonary Hypertension (REHIPED), from February to December 2016. The survey requested data about the site-specific protocol for AVT and subsequent management of pediatric patients with idiopathic pulmonary arterial hypertension (IPAH) or heritable PAH (HPAH). Twenty-eight centers from 13 countries answered the survey. AVT is performed in most centers using inhaled nitric oxide (iNO). Sitbon criteria was used in 39% of the centers, Barst criteria in 43%, and other criteria in 18%. First-line therapy for positive AVT responders in functional class (FC) I/II was calcium channel blocker (CCB) in 89%, but only in 68% as monotherapy. Most centers (71%) re-evaluated AVT-positive patients hemodynamics after 6-12 months; 29% of centers re-evaluated based only on clinical criteria. Most centers (64%) considered a good response as remaining in FC I or II, with near normalization of pulmonary arterial pressure and pulmonary vascular resistance, but a stable FC I/II alone was sufficient criteria in 25% of sites. Protocols and diagnostic criteria for AVT, and therapeutic approaches during follow-up, were highly variable across the world. Reported clinical practice is not fully congruent with current guidelines, suggesting the need for additional studies that better define the prognostic value of AVT for pediatric IPAH patients.
- 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.
article 0 Citação(ões) na Scopus Consenso sobre la clasificación de la enfermedad vascular pulmonar hipertensiva en niños: reporte del task force pediátrico del Pulmonary Vascular Research Institute (PVRI) Panamá 2011(2012) DEL CERRO, María Jesús; ABMAN, Steven; DÍAZ, Gabriel; HEATH FREUDENTHAL, Alexandra; FREUDENTHAL, Franz; HARIKRISHNAN, S; HAWORTH, Sheila G; DUNBAR, Ivy; LOPES, Antonio A; USHA RAJ, J; SANDOVAL, Julio; STENMARK, Kurt; ADATIA, IanCurrent classifications of pulmonary hypertension have contributed a great deal to our understanding of pulmonary vascular disease, facilitated drug trials, and improved our understanding of congenital heart disease in adult survivors. However, these classifications are not applicable readily to pediatric disease. The classification system that we propose is based firmly in clinical practice. The specific aims of this new system are to improve diagnostic strategies, to promote appropriate clinical investigation, to improve our understanding of disease pathogenesis, physiology and epidemiology, and to guide the development of human disease models in laboratory and animal studies. It should be also an educational resource. We emphasize the concepts of perinatal maladaptation, maldevelopment and pulmonary hypoplasia as causative factors in pediatric pulmonary hypertension. We highlight the importance of genetic, chromosomal and multiple congenital malformation syndromes in the presentation of pediatric pulmonary hypertension. We divide pediatric pulmonary hypertensive vascular disease into 10 broad categories.article 0 Citação(ões) na Scopus Clasificación funcional de la hipertensión pulmonar en niños: informe del task force pediátrico del Pulmonary Vascular Research Institute (PVRI), Panamá 2011(2012) LAMMERS, Astrid E; ADATIA, Ian; DEL CERRO, María Jesús; DÍAZ, Gabriel; HEATH FREUDENTHAL, Alexandra; FREUDENTHAL, Franz; HARIKRISHNAN, S; DUNBAR, Ivy; LOPES, Antonio A; USHA RAJ, J; SANDOVAL, Julio; STENMARK, Kurt; HAWORTH, Sheila GThe members of the Pediatric Task Force of the Pulmonary Vascular Research Institute (PVRI) were aware of the need to develop a functional classification of pulmonary hypertension in children. The proposed classification follows the same pattern and uses the same criteria as the Dana Point pulmonary hypertension specific classification for adults. Modifications were necessary for children, since age, physical growth and maturation influences the way in which the functional effects of a disease are expressed. It is essential to encapsulate a child's clinical status, to make it possible to review progress with time as he/she grows up, as consistently and as objectively as possible. Particularly in younger children we sought to include objective indicators such as thriving, need for supplemental feeds and the record of school or nursery attendance. This helps monitor the clinical course of events and response to treatment over the years. It also facilitates the development of treatment algorithms for children. We present a consensus paper on a functional classification system for children with pulmonary hypertension, discussed at the Annual Meeting of the PVRI in Panama City, February 2011.- Cardiac catheterization in children with pulmonary hypertensive vascular disease: consensus statement from the Pulmonary Vascular Research Institute, Pediatric and Congenital Heart Disease Task Forces(2016) CERRO, Maria Jesus del; MOLEDINA, Shahin; HAWORTH, Sheila G.; IVY, Dunbar; DABBAGH, Maha Al; BANJAR, Hanaa; DIAZ, Gabriel; HEATH-FREUDENTHAL, Alexandria; GALAL, Ahmed Nasser; HUMPL, Tilman; KULKARNI, Snehal; LOPES, Antonio; MOCUMBI, Ana Olga; PURI, G. D.; ROSSOUW, Beyra; HARIKRISHNAN, S.; SAXENA, Anita; UDO, Patience; CAICEDO, Lina; TAMIMI, Omar; ADATIA, IanCardiac catheterization is important in the diagnosis and risk stratification of pulmonary hypertensive vascular disease (PHVD) in children. Acute vasoreactivity testing provides key information about management, prognosis, therapeutic strategies, and efficacy. Data obtained at cardiac catheterization continue to play an important role in determining the surgical options for children with congenital heart disease and clinical evidence of increased pulmonary vascular resistance. The Pediatric and Congenital Heart Disease Task Forces of the Pulmonary Vascular Research Institute met to develop a consensus statement regarding indications for, conduct of, acute vasoreactivity testing with, and pitfalls and risks of cardiac catheterization in children with PHVD. This document contains the essentials of those discussions to provide a rationale for the hemodynamic assessment by cardiac catheterization of children with PHVD.
- Saudi guidelines on the diagnosis and treatment of pulmonary hypertension: 2014 updates(2014) IDREES, Majdy M.; SALEEMI, Sarfraz; AZEM, M. Ali; ALDAMMAS, Saleh; ALHAZMI, Manal; KHAN, Javid; GARI, Abdulgafour; ALDABBAGH, Maha; SAKKIJHA, Husam; ALDALAAN, Abdulla; ALNAJASHI, Khalid; ALHABEEB, Waleed; NIZAMI, Imran; KOUATLI, Amjad; CHEHAB, May; TAMIMI, Omar; BANJAR, Hanaa; KASHOUR, Tarek; LOPES, Antonio; MINAI, Omar; HASSOUN, Paul; PASHA, Qadar; MAYER, Eckhard; BUTROUS, Ghazwan; BHAGAVATHULA, Sastry; GHIO, Stefano; SWISTON, John; BOUEIZ, Adel; TONELLI, Adriano; LEVY, Robert D.; HOEPER, MariusThe Saudi Association for Pulmonary Hypertension (previously called Saudi Advisory Group for Pulmonary Hypertension) has published the first Saudi Guidelines on Diagnosis and Treatment of Pulmonary Arterial Hypertension back in 2008. ([1]) That guideline was very detailed and extensive and reviewed most aspects of pulmonary hypertension (PH). One of the disadvantages of such detailed guidelines is the difficulty that some of the readers who just want to get a quick guidance or looking for a specific piece of information might face. All efforts were made to develop this guideline in an easy-to-read form, making it very handy and helpful to clinicians dealing with PH patients to select the best management strategies for the typical patient suffering from a specific condition. This Guideline was designed to provide recommendations for problems frequently encountered by practicing clinicians involved in management of PH. This publication targets mainly adult and pediatric PH-treating physicians, but can also be used by other physicians interested in PH.
- 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.