Study On The Efficacy Of Pulmonary Hypertension Targeted Drugs After Surgery For Complex Congenital Heart Diseas

Objectives:Pulmonary hypertension associated with congenital heart disease is the most common type of pulmonary hypertension in China.The pulmonary hypertension associated with left-to-right shunt congenital heart disease has been through studied,and the indication and effect of targeted drugs for pulmonary hypertension have also obtained sufficient evidence in this type of patients.However,for patients with complex congenital heart disease complicated with pulmonary vascular diseases,such as segmental pulmonary hypertension and single ventricle-associated pulmonary vascular diseases,little research pays attention to whether targeted drugs can improve the conditions of these patients.Even more,after cardiac surgery,there is totally lack of research on whether targeted drugs can decrease the pulmonary arterial pressure,cause severe complications and improve the surgical outcome of these complex cardiac diseases.In this way,many drugs are used empirically rather than evidence-based.This study included patients with complex congenital heart disease complicated with pulmonary vascular diseases,with the purpose of providing evidence-based medical effect of targeted therapy for those patients.Methods:According to the different types of congenital heart disease and operation,the study was divided into three parts.The first part focused on the effect of inhaled nitric oxide in patients after corrective repair of cyanotic and pulmonary blood flow decreased congenital heart diseases.The second part paid attention to the inhospital prognosis of unifocalization and corrective repair with pulmonary atresia/ventricular septal defect with major aortopulmonary collateral arteries.The third part focused on the effects of intravenous Treprostinil in high-risk(mean pulmonary arterial pressure≥15mmHg)patients after total cavo-pulmonary connection.In the first part,we retrospectively investigated patients who get corrective repair of cyanotic and pulmonary blood follow decreased congenital heart disease with the ratio of right ventricular systolic pressure,systolic blood pressure>75%after weaned from cardiopulmonary bypass,and diagnosed with low cardiac output syndrome at intensive care unit in department of pediatric cardiac surgery of Fuwai hospital.Patients were separated into two groups,as combined therapy group(inhaled nitric oxide combined with conventional therapy)or conventional group(conventional therapy only).The incidence of low cardiac output syndrome and left atrial pressure during the first 24 hours after surgery and the in-hospital outcome between the two groups were investigated.In the second part,we retrospectively analyzed pediatric patients between 2014 and 2022 in the department of pediatric cardiac surgery of Fuwai hospital.The possible prognostic indicators included all commonly used clinical data.Unsatisfactory postoperative recovery was defined as who met at least one of the criteria:death and/or mechanical ventilation>7 days.Satisfactory postoperative recovery was defined as who met none of the above criteria.We separated patients into two groups and compared the peri-operative data through univariate analysis.In the third part,we retrospectively investigated patients who underwent high risk total cavo-pulmonary connection procedure and received the intravenous Treprostinil therapy in the department of pediatric cardiac surgery of Fuwai hospital from 2015 to 2022.The hemodynamics during the first 24 hours before and after maintaining dose of Treprostinil were investigated.Those patients were separated into two groups(satisfactory recovery group and delayed recovery group)based on whether the length of postoperative stay was no more than 30 days.The peri-operative parameters of the two groups were investigated to find possible indicators to improve the postoperative recovery.Results:In the first part,there were 79 patients,42 in conventional therapy group and 37 in combined therapy group.There was no difference between the two groups in demographic characteristics.In surgical parameters,the difference existed in the total neo-pulmonary artery index which showed that the pulmonary vascular disease in combined therapy group is more severe than that in conventional therapy group(p=0.007),which showed more severe pulmonary vascular disease in combined therapy group.By comparing the incidence of low cardiac output syndrome at each observation point within 24 hours after surgery,it was found that the combined treatment group was significantly lower than the conventional treatment group at 6 hours,12 hours and 18 hours(p<0.001 at 6 hours and 12 hours and p=0.004 at 18 hours).The incidence of low cardiac output syndrome in the combined treatment group was still lower than the conventional treatment group at 24 hours after surgery,however,the statistical difference was not significant(p=0.084).There was no significant increase in LAP during surveillance(n=20,p=0.817).Besides,we discovered that the need for renal replacement therapy was lower in the combined therapy group than conventional therapy group,especially in the moderate complicated(RACHS-1 category≤3)subgroup(P=0.024).In the second part,a total of 19 patients were included.There were 8 patients in unsatisfactory recovery group and 11 patients in satisfactory recovery group.Among all the possible prognostic indicators,through univariate analysis,only pulmonary arterial pressure in pulmonary flow study was statistically different(p=0.027).The ROC curve showed that the area under curve and cut-off values in predicting satisfactory recovery were 0.841 and 22 mmHg;the corresponding sensitivity and specificity were 100%and 72.7%.The targeted pulmonary hypertension drugs were unable to improve surgical outcomes in these patients.In the third part,24 patients were included.During the observation period,the mean pulmonary artery pressure decreased(p<0.001)with no severe complications.In analysis the possible prognostic indicators,there were 9 patients in satisfactory recovery group and 15 patients in delayed recovery group.There was no difference between the two groups in demographic characteristics and surgical parameters.However,there was statistical difference in the maintaining dose of Treprostinil between the two groups(p=0.027)through multivariable regression.The ROC curve showed that maintaining dose of Treprostinil>19.5 ng/kg/min was benefit to improve the postoperative recovery,with the area under curve 0.852,sensitivity 0.889 and specificity 0.8.Conclusions:The application of targeted pulmonary hypertension drugs in patients after corrective repair of cyanotic and pulmonary blood flow decreased congenital heart diseases can improve the incidence of low cardiac output syndrome and prognosis of patients,which benefit from better organ protection.In sub-group of RACHS-1≤3,it can reduce the occurrence of severe complications(renal replacement therapy).In Representative operation of RACHS-1 category>4,pulmonary arterial pressure<22 mmHg in pulmonary flow study can avoid unsatisfactory in-hospital recovery after unifocalization and corrective repair of pulmonary atresia/ventricular septal defect with major aortopulmonary collateral arteries.Pulmonary hypertension targeted drugs cannot improve prognosis in those extremely complex patients.In patients after high-risk total cavo-pulmonary connection procedure,the intravenous Treprostinil therapy can decrease mean pulmonary artery pressure without severe complication.A maintaining dose of Treprostinil>19.5 ng/kg/min was benefit to shorten the postoperative length of hospital stay and postoperative recovery in high-risk total cavo-pulmonary connection.