Study On Congenital Heart Disease Associated Arrhythmias And Its Genetic Factors Analysis

Background and Objective: Congenital heart diseases (CHD) arecardiovascular malformations caused by abnormal development during the period offetal. They are the most common birth defects and the leading cause of neonataldeath in China. With the continuous improvement of medical levels in these years,more patients with CHD thrive well in a longer life. But cardiac arrhythmias havebecome the most common complication in CHD patients, and result in asignificantly increased morbidity and mortality of adult CHD. The etiology of thesediseases is still not clear yet, but the importance of genetic factors has gradually beencognized. Due to higher incidence of CHD patients in Jiangxi province, types andincidence of arrhythmia in the patients will be systematically observed in this studyto see the condition of CHD induced arrhythmias in Jiangxi province.The geneticcauses will be further explored in order to provide theoretical basis to guide theprevention and treatment of CHD.Methods: We collected the clinical data and blood samples of the CHD patientswith arrhythmia. The selected CHD are atrial septal defect (ASD), ventricular septaldefect (VSD), patent ductus arteriosus (PDA), and other complicated CHD, such astetralogy of Fallot (TOF). To find the influence of CHD surgery on the arrhythmias,the types of arrhythmias and their incidence in different CHD were statisticallyanalyzed by the preoperative and postoperative electrocardiogram of selectedpatients. Several candidate ion channel genes that containing SCN5A, KCNH2(HERG), KCNQ1(KvLQT1), KCNJ2(Kir2.1), KCNE1(Mink) and KCNE2(MiRP1) were screened by using DNA direct sequencing. To reveal the genetictendency in CHD patients combined with arrhythmias.Results: There were totally682selected CHD patients that including255maleand427female. Among them,218patients had corrective surgery (32%) and464patients had transcatheter closure surgery (68%). According to the types of CHD,there were226ASD (33.1%),116PDA (17%),5TOF (0.7%) and335VSD (49.1%). In all selected patients,20patients had preoperative arrhythmias and162patientshad postoperative arrhythmias that accounting for2.9%and23.8%of the totalrespectively. The most common arrhythmias are atrial fibrillation (AFL), bundlebranch block (BBB) and atrioventricular block (AVB). According to the results ofstatistics, the incidence rate of arrhythmias in patients had transcatheter closuresurgery (17%) is much lower than those who had corrective surgery (38.1%) whilethe percentage is28.6%and40%-60%respectively from the publications at homeand abroad.We didn’t find any mutation by genetic screening of candidate genes amongCHD patients with malignant ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation,VT/VF), excepted for a synonymous single nucleotidepolymorphism(SNP) S546S in potassium ion channel coding genes KCNQ1， whichlocated in the13thexon with the1638thbase G changed into base A. The cellularelectrophysiological analysis showed that S546S-KCNQ1didn’t cause anyfunctional change in potassium channel，and there was no obvious change in thecurrent density voltage curve and voltage dependent of steady-state activation curvecompared with wild type by patch clamp, there was no statistically significantdifferences (P>0.05).Conclusion: The incidence of postoperative arrhythmias was obviously higherthan the rate of preoperative arrhythmias in child and adult CHD, which wasconsistent with the domestic and overseas data. Patients underwent correctivesurgery had lower incidence of arrhythmias compared with those who sufferedtranscatheter closure surgery, which implied that the prior one had lower rate ofcomplications.The incidence of malignant ventricular arrhythmias in CHD was low.The synonymous SNP S546S-KCNQ1might have no relationship with CHDinduced arrhythmias due to the results of cellular electrophysiological analysisshowed that S546S-KCNQ1didn’t cause any functional change.