Abstract 13558: Age-Dependent Change of Electrocardiographic Characteristics and Cardiac Events in the Long QT Syndrome Type-3 With E1784K Mutation of SCN5A

Abstract

Introduction: The pathogenic variant of E1784K in SCN5A is known as an overlapped phenotype; long-QT syndrome type-3 (LQT3) and Brugada syndrome (BrS), however it is still unclear age-dependent changes of the ECG findings and which ECG parameters are associated with cardiac events (CEs) in LQT3 patients with SCN5A -E1784K. Methods: Total 79 LQT3 patients with SCN5A -E1784K (45 probands, 42 males, age 23±17 years, QTc interval: 500±33 ms) were enrolled from the NCVC LQTS registry (2003~2023). We retrospectively evaluated age-dependent change of the clinical characteristics, ECG parameters and those associated with CEs. Results: Overall, 14 (18%) patients had CEs (10 syncope and 4 ventricular fibrillation), in which 8 occurred under 25 years old, but 6 occurred more than 35 years old. Thus, we divided all into two groups: younger (n=51) or older (n=28) than 30 years old. The younger group shows higher prevalence of male and proband compared with older group, and half of the syncope occurred during exercise. In the ECG parameters, P-R interval and QRS width were significantly longer in older group, in contrast, presence of T-wave alternance, notched, biphasic T-wave and bradycardia were more prevalent in younger group although the QTc interval and QTc peak-end were not different between the two group. Univariate analysis for CEs shows that longer QTc peak-end interval and absence of family history of LQTS are associated with CEs in younger group, whereas in older group, not only the longer QTc peak-end interval and absence of family history but also the Brugada ECG were associated with CEs. Finally, multivariate logistic regression analysis for all patients revealed that longer P-R interval, QTc peak-end and absence of family history of LQTS were independently associated with CEs (p=0.049, p<0.001, p=0.001, respectively). ROC analysis revealed that P-R interval ≥180 ms and QTc peak-end interval ≥86 ms were significantly related to previous CEs. Conclusion: In LQT3 with SCN5A -E1784K variant, ECG parameters were age-dependently altered and longer P-R and QTc peak-end interval as well as absence of family history of LQTS can be associated with CEs. Furthermore, in adult patients, more careful follow-up should be required for those with LQT3 overlapped with BrS ECG.