Arrhythmic risk during pregnancy and postpartum in patients with long QT syndrome

Congenital long QT syndrome (LQTS) is a genetic disorder characterized by a prolonged QT interval in the surface electrocardiogram (ECG) that predisposes affected individuals to arrhythmic syncope, ventricular torsades-de-pointes, and sudden cardiac death at a young age. Investigations of large patient cohorts revealed sex-related differences in the LQTS phenotype. Adult women with LQTS are at higher risk for cardiac arrhythmias than are adult men with LQTS. Sex hormones are thought to play the primary role for these gender differences. Clinical experience and translational studies indicated that females with LQTS have a lower risk for cardiac arrhythmias during pregnancy and elevated risk in the postpartum period due to contrasting effects of estradiol and progesterone, as well as postpartum hormones on the action potential and arrhythmia substrate. However, this pro- or anti-arrhythmic potential of hormones varies depending on the underlying genotype, partly since sex hormones have distinct effects on different (affected) cardiac ion channels. Thus, a comprehensive evaluation of women with LQTS prior to and during pregnancy, during labor, and in the postpartum period with consideration of the patient's disease- and gene-specific risk factors is essential to providing precision management in this patient group. This review discusses the current understanding of hormonal influences in LQTS and provides practical guidance for the optimal management of LQTS patients during pregnancy, delivery, and the postpartum period.