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Combined clinical and surgical approaches to congenital heart disease associated with pulmonary arterial hypertension - possible role of genetic and inflammatory markers

Abstract

Pulmonary arterial hypertension (PAH) is a complicating factor in the management of congenital heart disease (CHD) with intracardiac or extracardiac shunts. In children with moderate to severe PAH, the risk of serious complications following the surgical repair of shunts (including right cardiac failure and death) is 15% to 20%, and the risk of late, postoperative residual PAH is up to 25%. We therefore intend to conduct a study aimed at: 1- reducing the risk of immediate postoperative complications to less than 10%; 2- reducing the likelihood of late postoperative (residual) PAH to less than 10% in children with moderate PAH; 3- promoting a significant reduction in pulmonary artery pressure and vascular resistance, at six month postoperatively, in children with moderate to severe PAH. We hypothesized that these goals could be achieved by treating patients preoperatively and for six months postoperatively with sildenafil, either singly or combined with bosentan. Both drugs have been approved for treatment of PAH on the basis of randomized clinical trials. Preoperative and postoperative (on treatment) hemodynamic evaluation will be based on noninvasive and invasive diagnostic procedures. As a second objective, we intend to analyse possible abnormalities in three genes that have been associated with PAH in CHD, and 36 inflammatory mediators. The idea is to investigate whether changes in these biomarkers correlate with the response to combined medical and surgical treatments. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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 AUGUSTO. Parameters associated with outcome in pediatric patients with congenital heart disease and pulmonary hypertension subjected to combined vasodilator and surgical treatments. PULMONARY CIRCULATION, v. 9, n. 3 JUL 2019. Web of Science Citations: 0.
MAEDA, NAIR Y.; AIELLO, VERA D.; SANTOS, PAULO C.; THOMAZ, ANA M.; KAJITA, LUIZ J.; BYDLOWSKI, SERGIO P.; LOPES, ANTONIO AUGUSTO. Relation of Macrophage Migration Inhibitory Factor to Pulmonary Hemodynamics and Vascular Structure and Carbamyl-Phosphate Synthetase I Genetic Variations in Pediatric Patients with Congenital Cardiac Shunts. Mediators of Inflammation, 2019. Web of Science Citations: 1.
ZORZANELLI, LEINA; MAEDA, NAIR; CLAVE, MARIANA; THOMAZ, ANA; GALAS, FILOMENA; RABINOVITCH, MARLENE; LOPES, ANTONIO. Relation of Cytokine Profile to Clinical and Hemodynamic Features in Young Patients With Congenital Heart Disease and Pulmonary Hypertension. AMERICAN JOURNAL OF CARDIOLOGY, v. 119, n. 1, p. 119-125, JAN 1 2017. Web of Science Citations: 5.
ZORZANELLI, LEINA; MAEDA, NAIR YUKIE; CLAVE, MARIANA MEIRA; AIELLO, VERA DEMARCHI; RABINOVITCH, MARLENE; LOPES, ANTONIO AUGUSTO. Serum Cytokines in Young Pediatric Patients with Congenital Cardiac Shunts and Altered Pulmonary Hemodynamics. Mediators of Inflammation, 2016. Web of Science Citations: 1.

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