Arterial Switch Operation Around The Perioperative Risk Factors Analysis And Bosentan In The Treatment Of Postoperative Pulmonary Hypertension Clinical Study

PartⅠCurrent risk factors influencing early mortality of the arteraal switch operattionObjective:The present study analyses the result of the arterial switch operation (ASO)for transposition of the great arteries and Taussig-Bing in our hospital from 2001-2008. To determine the independent risk factors for early mortality and morbidity on arterial switch operation,and identify the reasons of decreasing mortality in recent years. Background:In West, there had a lot of reports on risk factors affecting outcome of the ASO. But in China, we started to do ASO later and the characteristics of patients were different from other countries'. We have been never evaluated the independent risk factors for early mortality and morbidity on ASO. So identify predictors of early mortality and morbidity on ASO become more and more important for us to advance our medical skill.Method:258 patients who-underwent ASO at our hospital between January 1,2001 and December 31,2008 were included. Hospital charts, operative reports, echocardiographic and cardiac catheterization datas of all patients were reviewed. Demographics, preoperative, intraoperative and postoperative variables were recorded.Result:258 patients were included in the study (median age at ASO=90d and median weight=5kg). HGB was 154±34g/l,and SPaO2 was 73±14%.165 (64%) patients had ventricular septal defect, including 47 Taussig-Bing anomaly, others had intact ventricular septum. Coronary anatomy was normal in 188(73%) patients (1LCx2R), others were abnormal including 18 single coronary,7 intramural patterns. The position of the great arteries (aorta in relation to the PA) was anterior and rightward in 175(68%) patients, anterior/posterior in 31(12%) patients, side by side in 16(6%) and anterior and leftward in 36(14%). Other complications included aortic arch obstruction or interruption in 10, valve regurgitation in 14 cases and mild left ventricular outlet obstruction in 12cases. In preoperational time,15% patients received prostaglandin, and left ventricle training was performed in 19 patients. The ASO was performed via median sternotomy. CPB was established and maintained at flow rates of 50ml/kg/min and temperatures between 18-22℃. ThePB time was 203±57 minutes and aortic cross-clamp time was 134±40 minutes. Median ventilation time was 3 days (0-83days), and intensive care unit stay was 10 days (0-117days).There were 26 hospital deaths (operative mortality was 10.1%), in recently (2006-2008) the operative mortality was decreased to 4%. The main complications of post-operation included.27(10%) delayed sternal closure,42(16%) low cardiac output,25(9.7%) renal dysfunction required peritoneal dialysis, and 49(19%) prlonged ventilation support. Multivariate logistic regression analysis revealed that poor coronary arteries transplant location (P=0.003,OR=29), unusual coronary arteries pattern (P=0;001,OR=23.4) and age at operation younger than 6 months (P=0.03,OR=6.2) were independent predictors of early mortality in past time(2001-2005). Howerever, few patients died nowdays,so no factors was associated with increased operative risk. Reasons of deadly decreasiong in mortality were inprovements of coronary arteries transplant technique, CPB technique, and ICU technique. But poor coronary arteries transplant location were independent predictors of post-operative low cardiac output and renal dysfunction. Associated with aortic arch pathology were independent predictors of delayed ventilation time recently (2006-2008).Conclusion:The ASO can be performed in our hospital current era with low early mortality. Coronary arteries transplant carefully remain as challenges to optimize morbidity for the arterial switch operation. PartⅡ:Treatment of patients with bosentan in post-operation of congenital heart disease with pulmonary arterial hypertension:a doubie-blnd, randomized controlled trialBackground and objective:Endothelin is a 21-aminoacid peptide that has a key role in the pathogenic of pulmonary arterial hypertension. High concentrations of endothelin-1 have been recorded in plasma and lungs of patients with pulmonary artery hypertension associated with congenital heart disease, and the concentrations of endothelin-1 was correlated with severity degree of pulmonary arterial disease. Endothelin exerting vasoconstrictor and mitogenic effects by binding to two distinct receptor isoforms in the pulmonary vascular smooth muscle cells:endothelin A and B receptors. Bosentan is an orally active dual (A and B) endothelin receptor antagonist that has been shown to improve exercise capacity, haemodynamics, and clinical worsening in many clinical trials, but have no experience in post-operation of congenital heart disease with PAH. In our country, there are lots of elder patients of congenital heart disease accompany with pulmonary arterial hypertension. And they have poor prognosis after operation because pulmonary arterial hypertension leads to right ventricular failure and sudden death. So we hope bosentan can improve clinical outcome of these.patients. This time we present the results of the bosentan trial in post-operative patients still with pulmonary arterial hypertension, a randomized controlled trial designed to assess the efficacy and safety of the dual endothelin receptor antagonist bosentan in post-operative pulmonary arterial hypertension, and present the first experience of bosentan for infants.Methods:This study was a prospective clinical trial.The objects were 30 patients (age:4m-6.8y,weight:5-15kg) who still had pulmonary artery hypertension at one week after cardiac defects repaired. They were randomized to controlled (n=15) or to bosentan (n=15). Dosage regimen:10-20kg patients,31.25mg qd(4w),31.25mg bid(8w);5-10kg patients,15.6mg qd(4w),15.6mgbid(8w). Evaluate the efficacy and safety of Bosentan through the amelioration of pulmonary arterial systolic pressure, WHO functional class, and clinical worsening. Investigate the associated factors with pulmonary artery hypertension.Results:We monitored pulmonary arterial systolic pressure after operation by echocardiogram 2 times, baseline (1 week after operation) and at 12 weeks later. The pulmonary arterial systolic pressure decreased 19.5 mmHg in Bosentan group(P=0.000), and decreased 10.3 mmHg in control group (P=0.164), with the mean treatment effect of 9.2mmHg (P=0.:049,95%CI:0.1-18.3). The effct of bosentan on haemodynamics is also reflected in the reduction plasma ET-1 concentration in bosentan group.Plasma ET-1 in control group increased 0.15±0.1fmol/ml(P=0.77),however, decreased 2.01±0.3fmol/ml (P=0.03) in bosentan group; Bosentan prevented post-operation PAH.Bosentan treatment was associated with lower incidence of worsening NYHA functional class compared with controlled(0%in:the bosentan group vs 13% in the placebo group, p=0.02) There was a delay in time;to clinical worsening with bosentan compared wih controlled group.Age of operation was tightly correlated topulmonary hypertension. Abnormal liver function occurred in 2 cases in Bosentan group but resolved after discontinuation of Bosentan treatment, no other side effects. Bosentan produced hemodynamic improvement and was well tolerated in infant.Conclusions:Bosentan administration in patients with postoperative PAH is safe and efficient. Bosentan is a new effective approach to therapy for postoperative pulmonary,arterial hypertension in children.