Long QT and Gender

Source: Lehmann MH, et al. J Am Coll Cardiol 1997;29:93-99.
It is well known that the corrected electrocardiographic QT interval (QTc) is shorter in men than women and that women are more susceptible to torsade de pointes. Lehmann et al investigated whether this gender difference persists in patients with the congenital long QT syndromes.

They analyzed QTc by age and gender in 460 genotyped blood relatives from families with long QT syndromes related to chromosomes 11p, 7q, or 3p. The QTc in 240 non-affected members was shortest in men 405 ± 23 msec and longest in women and children (age < 16) 420 ± 23 (P < 0.001). This difference persisted in the affected members with 7q and 11p (n = 194) but not 3p (n = 26): 473 ± 33 men vs. 490 ± 45 women (P < 0.02). Multiple regression analyses identified genotype and age-gender group as predictors of QTc.

Interestingly, the absolute QT interval difference between men and women was greatest at heart rates less than 60 beats/min. The authors conclude that men must possess a factor that blunts QT prolongation, especially at slow heart rates, and protects them from torsade de pointes. Since this phenomenon is only apparent after puberty, it is tempting to assume it is androgen. If so, it is the only known positive effect of androgens on the cardiovascular system.

The fact that QT shortening in men is most evident at slow heart rates probably explains their relative resistance to torsade de pointes since this arrhythmia is facilitated by the QT lengthening of bradycardia. The lack of QTc shortening in men affected with the 3p defect may be due to small numbers or some unique feature of this defect. Since at least eight different potassium channels have been identified in animals, more work needs to be done in humans to fully characterize the long QT syndromes. However, most human cases genotyped to date have been of the 7q and 11p potassium channel mutations.—mhc