Age at Menarche and the Risk of Cardiac Events in Women With Congenital Long QT Syndrome

Background Women with congenital long‐QT syndrome (LQTS) experience increased risk of cardiac events (CE) after the onset of adolescence, possibly due to the effect of sex hormones on the cardiac ion channels. We hypothesized that late menarche may affect the risk of CE in women with LQTS. Methods Beginning in 2010, information on age at menses onset was obtained from all women enrolled in the Rochester LQTS Registry. Multivariable modeling was employed to evaluate the association of age at menarche with the burden of CE (total number of syncope, aborted cardiac arrest, and LQTS‐related sudden cardiac death) during the subsequent 20 years of follow‐up. Menarche groups were defined as early (<12 years), normal (12–16 years), and late (>16 years). Results We report data on 435 genetically confirmed LQTS women, of whom 68, 346, and 21 were in the early, normal, and late‐onset groups, respectively. The mean cumulative rate of CE at 20 years of follow‐up in women with late menarche was 28% and 64% higher than in women with normal or early menarche, respectively; P <0.001 for the overall difference during follow‐up. Consistently, multivariable analysis showed that late menarche was associated with a pronounced 52% increased risk of CE compared with normal menarche ( P =0.02). Conclusions Late menarche is associated with increased risk of CE in women with congenital LQTS. Further research is warranted to validate these findings and ascertain the explanatory pathophysiological pathways.