Abstract 12882: Risk Prediction in Adolescent Males With Congenital Long QT Syndrome

Introduction: Men and women with either type 1 (LQT1) or type 2 (LQT2) congenital long QT syndrome (LQTS) exhibit differential risk of cardiac events (CEs) after the onset of adolescence. Hypothesis: We have recently reported a novel prediction model for LQTS women after the onset of adolescence. We now report a risk prediction model for adolescents LQT1 or LQT2 males that integrates genotype-phenotype data. Methods: The prognostic model was derived from the Rochester LQTS Registry through March 2021, comprising 611 males with LQT1 (N=304) and LQT2 (N=307) from age 10 through 20 years. Anderson-Gill modeling was employed to develop risk groups for the endpoint of non-terminal CEs (total number of syncope, aborted cardiac arrest [ACA], and appropriate ICD shocks). The covariates in the CE model were then applied to the endpoint of a first life-threatening event (LTE: ACA, LQTS-related SCD, or appropriate ICD shocks). The prediction model included the following prespecified variables: genotype/mutation-locations, QTc-specific thresholds, history of syncope prior to 10 years of age, and time-dependent beta-blocker therapy. Results: During a total follow-up duration of 6048 patient-years, there were a total of 270 non-terminal CEs. The risk-prediction model identified three risk-groups based on genotype-phenotype variables (Figure). Compared with the Low-Risk group, High-Risk patients experienced a pronounced 5.2-fold (p<0.001) increased risk of CEs; Intermediate-Risk patients had a 2.1-fold (p=0.004) risk-increase. The 10-year rates of a first LTE for the Low- Intermediate- and High-Risk groups were 2%, 6%, and 8%, respectively. C-statistic for the CE prediction model was 0.61 (0.56-0.67). Conclusions: This is the first risk-prediction model that provides risk-estimates for CE and LTE in adolescent males with either LQT1 or LQT2 based on personalized genotype-phenotype data. The projected risk estimates can be used to guide sex-specific management in LQTS.