Long-term Follow-up Of Patients With Congenital Long QT Syndrome2from The Same Family Pedigree

Objective: To investigate the clinical manifestations, nature history andelectrocardiogram characteristics of the patients with congenital Long QT Syndrome2from the same family pedigree during the14years of long-term follow-up. To evaluatethe correlation between phenotype and genotype and describe the frequency of syncope,the occurrences of sudden cardiac death, changes of QT interval and QT dispersion ofpatients with LQT2. To elucidate the change trends of clinical characteristics of patientswith incomplete penetrance and patients with negative genotype.Methods:The routine clinical examination, ECG recordings and echocardiographyhave been done among26family members in1999. QT interval, QTc and QTdispersion have been measured. Diagnostic criteria for LQTS were defined by Schwartzin1999. DNA has extracted from the blood samples of26family members of theregistered study, and genetic testing revealed a nonsense mutation(CGA2587TGA) ofHERG gene in2011. As a result, genetic diagnosis was LQT2. Patients with syncopewere recommended to take propranolol hydrochloride. The dosage of propranolol was1mg/kg. Patients with the indication were advised to implant ICD based on theguidelines. All patients were educated to avoid trigger factors of cardiac events,prohibited patients from doing athletic activities, advised patients not to be alone andsleep alone, and members of the family were trained to do cardiopulmonaryresuscitation (CPR). Telephone follow-up1-2times a year, patients were admitted to thehospital with any recurrence of symptoms. ECG recordings were done every five years. The family survey was redone with the routine clinical examination, physicalexamination, ECG recordings respectively in2008and in2013. Treatments wererevised carefully.Results:1）7patients(27%) with positive clinical diagnosis and positive genetic diagnosis ofLQT2among25family members,5females and2males;11patients with suspiciouspositive clinical diagnosis and negative genetic diagnosis,9females,2males;8members with negative clinical diagnosis and negative genetic diagnosis.2) The triggers of syncope were emotional and physical stress in LQT2patients.The main ECG characteristics of LQT2revealed QTc≧460ms， which was moreobvious in severe patients, a broad and bimodal and notched T wave. U wave wereoften noticed.3) The occurrences and the frequency of syncope are related to age, sex andgenotype.6out of7patients with positive phenotype and positive genotype hadsyncope when they were enrolled,2males,4females. Age of the first attack is21±9;During follow-up,2male patients with previous syncope have no occur any more,4female patients often experienced syncope,2of them had torsade de pointes (Tdp)attack with aborted cardiac arrest, but they refused to ICD implantation. The syncopeepisodes decreased in2patients with irregularly propranolol administration. Theepisode increased after the discontinuous propranolol administration. No syncope wasdetected after continuous propranolol administration in the last6years follow-up.Patients with suspicious positive clinical diagnosis and negative genetic diagnosis, andmembers with negative clinical diagnosis and negative genetic diagnosis had nosyncope and amaurosis during follow-up.2cases death,1natural death and1died ofpulmonary cancer, and none of the family member experienced sudden cardiac death.4） QTc intervals are aggressively prolonged as LQT2patients get aged. It isobviously prolonged before TdP and cut down after the attack. In1999, the QTc of the patients with positive clinical diagnosis and positive genetic diagnosis is460±10ms, theQT dispersion is90±50ms. In2008,the QTc is470±10ms. The QT dispersion is100±40ms. In2013, the QTc is500±30ms. The QT dispersion is110±60ms. QTcinterval of LQT2patients in2013is longer than that in2013, but there is no statisticdifference between that in1999and that in2008.5) In1999,the QTc of the patients with suspicious positive clinical diagnosis andnegative genetic diagnosis is410±20ms,the QT dispersion is50±20ms.In1999,the QTcof the patients with negative cinical diagnosis and negative genetic diagnosis is400±10ms,the QT is40±20ms.6）There is a statistic difference of the QTc among LQT2patients and the othergroups which are susceptive positive phenotype group(susceptive group) and negativephenotype and negative genotype group(normal group). There is no statistics differenceof the QTc interval between the other two groups. There is no statistic difference of PRinterval, QRS duration among the three groups.Conclusion:1.The genetic diagnosis of the LQT2is well corrected with clinical diagnosis. Theclinical characteristics and risk factors for cardiac events in LQT2patients are related tothe age, gender, QTc duration, history of syncope and positive genotype.2.The main ECG characteristics of the LQT2family were included QTc≧460ms，and a broad and bimodal and notched T wave, U wave was noticed. The QT interval ofpatients with cardiac events is longer than that of those without cardiac events.3.There is a tendency of QTc prolongation as the LQT2patients get aged, but it isrelatively stable in a long time. The QTc interval is prolonged obviously just before Tdpand cut down after the episode attack.4.β-blocker could prevent LQT2patients from syncope effectively. Patients shouldbe educated to avoid trigger factors of cardiac evens and avoid from exposing to QT prologation drugs, Families should be trained with cardiac pulmonary resuscitation,which are as important as drug treatment.5.The family pedigree investigation combined with Clinical diagnosis and geneticdiagnosis plays an important role in study of the pathogenesis of LQTS, and may shedthe light on the LQTS gene therapy in the future.