Long QT syndrome. Why does sex matter?

There is increased awareness of the extent to which cardiac function is influenced by gender. One of the most dramatic and potentially lethal differences is that seen in cardiac repolarization reflected in the QT interval of the surface ECG. Gender differences in QT and QTc intervals have been observed to change during the lifetime in the general population. These differences can be explained to a large extent by sex hormone driven differences in gene expression of myocardial ion channels. Numerous studies have shown that women's risk to suffer arrhythmias in the context of QT prolonging drugs is doubled compared to men. For familial long QT syndrome there is no conclusive evidence for gender effects with respect to disease onset or mortality. Only subgroup analysis by genotype demonstrated a higher risk in female patients carrying mutations in the LQT2 locus. Special attention should be given to drug-induced QT prolongation in women.