Abstract 18157: Temporal Trends in Sex-Related Risk of Cardiac Events in Children With Congenital Long-QT Syndrome

Introduction: Unexplained male predominance during childhood until puberty is observed in long-QT syndrome (LQTS). As cardiac events in LQTS have been linked to the degree of physical activity, we hypothesized that the sex differential previously described may be attenuated by temporal trends in the level of activity in males and females with LQTS during childhood.

Methods: The study population comprised 1,356 patients from the Rochester LQTS Registry with LQTS Types 1, 2, or 3 (genetically confirmed or retrospectively identified phenotype positive family members of a genotype positive subject) with follow-up from birth through 14 years. Based on their year of birth, patients were divided into 3 groups by vicennium: 1960-1979, 1980-1999, and 2000-2021. The primary endpoint was a CE defined as nonfatal cardiac arrest, unexplained sudden death, appropriate implantable cardioverter defibrillator shock, or syncope. The age-related incidence of a first CE in each vicennium, with birth used as the time of origin, was determined by the Kaplan-Meier method. The hazard ratio (HR) of experiencing a first CE by sex was calculated using multivariate Cox-regression analysis.

Results: In the 1960-1979 cohort the incidence of first CE at age 14 was 28% versus (vs) 14% in boys vs girls, respectively (p<0.001 for the overall difference during follow-up [Figure left panel]). This difference was attenuated in the 1980-1999 cohort as the incidence was 30% vs 25% in boys vs girls, respectively (p=0.150 for the overall difference during follow-up [Figure center panel]). In the 2000-2021 cohort, event rates were lower and the incidence of a CE was similar in both boys and girls (18%; Figure right panel). The HRs for boys vs girls were 2.31 (p<0.001), 1.07 (p=0.684), and 0.95 (p=0.880) in the first, second, and third vicennium, respectively.

Conclusions: The strength of sex as a risk factor for cardiac events appears attenuated in contemporary populations of children with LQTS.