Retrospective Clinical Study And Genome-Wide Copy Number Variants Analysis On Congenital Pulmonary Atresia With Ventricular Septal Defect

Congenital heart disease(CHD) is the most common birth defect and the primary reason of non-infective death in baby term. Most chds belong to structural heart disease and can be divided into two categories: simple CHD and complex CHD. Pulmonary atresia with ventricular septal defect(PAVSD) belongs to the latter.From surgical perspective, state of the art for simple CHD in our country is approaching, or say, abreast with that in the western countries. But with respect to complex congenital heart disease, we have still a long way to catch up with, especially for PAVSD. Even in the western countries, the outcome of surgical treatment in PAVSD is not so optimistic.From etiological perspective, CHD is resulted from a combined effect of environment and genetics. Even in 10 years ago, we human know little about the genetic mechanism of CHD except for some genetic syndromes. At present, though we have achieved a lot in molecular genetics, how genetics and environment interact with each other and what the mechanism and pathways are like is still unknown. With regard to PAVSD, what we know at present is that the defect is linked closely with 22q11 deletion syndrome. Researchers have found evidence of 22q11 deletion syndrome in 30-50% of patient with PAVSD.This study is consisting of two parts:clinical and genetical. The surgical classification, strategy and probable abnormal genes or mutant loci of DNA.Part IRetrospective Clinical Study on Surgical Management of Congenital Pulmonary Atresia with ventricularseptal DefectObjective:we retrospectively collected and analyzed the data of a consecutive PAVSD patient which had been managed surgically in order trying to find some implication of the classification and surgical strategy of this population. Also we made a comparison among the several palliative and corrective types of procedure to find out which ones are superior over the others.Methods:the patients which had been managed surgically were with specific data of echocardiography and cardioangiography in the department of paediatric heart surgery of fuwai hospital All the patient had clear diagnoses and were indicated to surgery. The data of them during staying in hospital and follow-up were collected and analyzed retrospectively using epidemiological and statistical techniques and methods. The different palliative and corrective procedures were compared with each other in surgical early and mid-term outcome. The risk factors for surgery, survival rate and prognsis of the population were analyzed. Results:there were totally 195 case(108 males,87 females) who had underwent surgery from September,1998 to September,2008 in fuwai hospital, consisting of 131 of type I,58 of type II and 6 of type III cases(classification from Congenital Heart Surgery Nomenclature and Database Project). There were 22 surgical deaths and 7 late deaths during follow-up. Ninty-three cases had underwent aorto-pulmonary shunt or palliative reconstruction of right ventricular-pulmonary connection. The rate of patient finally surgically corrected among them were 28.1% for modified Blalock-Taussig shunt,7.1% for central shunt and 66.7% for right ventricular-pulmonary reconstruction, respectively. Ten cases died during the two perioperative terms, one case died during follow-up. One-stage corrective surgery were performed in 74 cases(unifocaliztion no included), including 40 males and 34 females, aged from 8 months to 27 years (median:2.6 years). They can be divided into 3 groups by types of procedure, patch:35 cases, conduit:28 cases, end-to-end anastomosis with patch:11 cases. There was no statistical difference among there three groups early after operation. There were 2,3 and 0 cases of early death for the three groups, respectively. Univariate analysis indicated CPB time, mcgoon ratio and Nakata index as risk factors for surgery. Multivariate analysis suggested CPB time was a risk factor. Echocardiography showed that the systolic pulmonary blood flow velocity in patch and end-to-end anastomosis with patch were statistically lower than that in conduit group (p<0.05) while no difference of pulmonary regurgitation among the three groups.Conclusion:The surgical mortality of PAVSD is still high. The development of from the main pulmonary trunk to the pulmonary tree into the lung is the most important indication for surgery. Hybrid intervention may be taken advantage of in some of these patients. One stage repair of PAVSD should only be warranted when conforming with strict indication. Surgeons should prudently choose procedures according to the development of pulmonary arteries. The end-to-end anastomosis with patch procedure which avoids usage of conduits may be performed in appropriate patients to achieve better early and mid-term result. But longer follow-up is mandatory to find out long-term outcome.Partâ…¡Genome-Wide Copy Number Variants Analysis on Congenital Pulmonary Atresia with ventricularseptal DefectObjective:to explore the application of genome-wide copy number variants analysis on the genetics of congenital heart disease.Methods:11 cases of pulmonary atresia with ventricular septal defect diagnosed in Fuwai hospital during June,2009 and December, 2009 were enrolled and blood samples were draw. Gdna of the samples were extracted and test with genome-wide copy number variations(CNVs) chip. Results:all 11 subjects were verified as isololated PAVSD patients.10 of which were found normal in extraction of gdna. There was no identical CNVs gain or loss among the patients. A 22q11 deletion was found in one patient and different gain or loss for 5 of them..Conclusion:Congenital heart defects have a genetic nature of heterogeneity. The methord of genome-wide scan for CNV is a promising tenique to explore the genetic mechanism of congenital heart diseases. The novel CNVs found in this study is to be test further to find out if it is morbigenous.