Combined clinical and surgical approaches to congenital heart disease associated w...
| Grant number: | 15/21587-5 |
| Support type: | Regular Research Grants |
| Duration: | December 01, 2016 - November 30, 2018 |
| Field of knowledge: | Health Sciences - Medicine |
| Principal Investigator: | Antonio Augusto Barbosa Lopes |
| Grantee: | Antonio Augusto Barbosa Lopes |
| Home Institution: | Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Assoc. researchers: | Claudia Regina Pinheiro Castro Grau ; Filomena Regina Barbosa Gomes Galas ; Marcelo Biscegli Jatene ; Maria Francilene Silva Souza ; Nair Yukie Maeda |
Abstract
Severe cardiopulmonary hemodynamic disturbances may complicate the postoperative course in young pediatric patients undergoing surgery for repair of congenital cardiac septal defects, even after successful operation. Initially, it was considered that such disturbances were essentially the result of pulmonary vasoreactive response (vasoconstriction) associated with a number of perioperative insults (so called pulmonary hypertensive crises - PHC), associated with a ~20-30% mortality). The current belief is that both the heart (particularly the right ventricle) and the pulmonary circulation play a role. Dysfunctional right heart with diminished cardiac output may predispose do PHC. Alternatively, PHC may further contribute to right heart functional deterioration and failure postoperatively. The hypothesis to be tested in this study is that the magnitude of the inflammatory response associated with cardiopulmonary bypass correlates with critical life-threatening postoperative cardiopulmonary events.The methodology will involve essentially the comparative analysis of two study groups: subjects with and subjects without critical postoperative events. These are defined as: 1- pulmonary vascular tone instability, characterized by hemodynamic, oximetric and metabolic assessments; 2- residual moderate to severe cardiac dysfunction (in particular, right cardiac dysfunction) to be assessed by transthoracic echocardiography. The following factors will be analyzed for possible correlation with postoperative events: 1- post-cardiopulmonary bypass inflammatory reaction to be assessed by measuring soluble and cellular markers of inflammation; 2- preoperative clinical presentation: emphasis to elements that suggest a high-risk phenotype in terms of pulmonary vascular resistance and pulmonary vascular tone instability; 3- preoperative pulmonary hemodynamics assessed noninvasively (Doppler echocardiography, all patients) and invasively (cardiac catheterization, when indicated); 4- intraoperative data including the duration of cardiopulmonary bypass assistance and pulmonary and systemic hemodynamics just after.The potential impacts of the present investigation seem obvious. The study endpoints (namely postoperative pulmonary vascular instability with PHC and residual moderate to severe right heart dysfunction) are largely associated with high mortality rates. In patients who survive, they are associated with prolonged mechanical ventilation and use of inhaled nitric oxide, prolonged ICU stay and prolonged (high-cost) hospitalization. Understanding the underlying mechanisms of these events is crucial for establishing appropriate therapeutic strategies. (AU)