Sex and gender aspects in antiarrhythmic therapy

Although cardiac arrhythmia had long been considered a predominantly male syndrome, it is now clear that arrhythmia is also a primary cause of mortality in women. Notably, the manifestation of specific arrhythmia syndromes appears to be gender specific. In particular, female sex is an independent risk factor for development of torsade de pointes (TdP) arrhythmias not only in congenital long QT syndromes but also in acquired long QT syndromes which occur as adverse effects of existing drugs. Males, on the other hand, are more likely to develop Brugada syndrome. Recent clinical and experimental studies suggest that these differences may stem from intrinsic sex differences in cardiac tissue. These include fundamental electrical differences resulting from variable ion channel expression and diverse sex hormonal regulation via long-term genomic and acute nongenomic pathways, and sex differences in drug responses and metabolisms. Undoubtedly, determining the effect of gender on cardiac function will be difficult and require sophisticated methodologies. However, gender differences underlying predilection to distinct arrhythmia syndromes must be revealed so that new therapeutic strategies that take gender into account can be applied to at-risk patients.