AGE-GENDER INFLUENCE ON THE RATE-CORRECTED QT INTERVAL AND THE QT-HEART RATE RELATION IN FAMILIES WITH GENOTYPICALLY CHARACTERIZED LONG QT SYNDROME

Objectives. We sought to analyze age-gender differences in the rate-co rrected QT (QTc) interval in the presence of a QT-prolonging gene. Bac kground. Compared with men, women exhibit a longer QTc interval and an increased propensity toward torsade de pointes. In normal subjects, t he QTc gender difference reflects QTc interval shortening in men durin g adolescence. Methods. QTc intervals were analyzed according to age ( <16 or greater than or equal to 16 years) and gender in 460 genotyped blood relatives from families with long QT syndrome linked to chromoso me 11p (KVLQT1; n = 199), 7q (HERG; n = 208) or 3p (SCN5A; n = 53). Re sults. The mean QTc interval in genotype negative blood relatives (n = 240) was shortest in men, but similar among women, boys and girls. Fo r genotype positive blood relatives, men exhibited the shortest mean Q Tc interval in chromosome 7q- and 11p-Iinked blood relatives (n = 194) , but not in the smaller 3p-linked group (n = 26). Among pooled 7q- an d 11p-linked blood relatives, multiple regression analysis identified both genotype (p < 0.001) and age-gender group (men vs. women/children ; p < 0.001) as significant predictors of the QTc interval; and heart rate (p < 0.001), genotype (p < 0.001) and age-gender group (p 0.01) a s significant predictors of the absolute QT interval. A shorter mean Q T interval in men was most evident for heart rates <60 beats/min. Conc lusions. In familial long QT syndrome linked to either chromosome 7q o r 11p, men exhibit shorter mean QTc values than both women and childre n, for both genotype-positive and -negative blood relatives. Thus, adu lt gender differences in propensity toward torsade de pointes may refl ect the relatively greater presence in men of a factor that blunts QT prolongation responses, especially at stow heart rates.