Age-gender influence on the rate-corrected QT interval and the QT-heart rate relation in families with genotypically characterized long QT syndrome

J Am Coll Cardiol. 1997 Jan;29(1):93-9. doi: 10.1016/s0735-1097(96)00454-8.


Objectives: We sought to analyze age-gender differences in the rate-corrected QT (QTc) interval in the presence of a QT-prolonging gene.

Background: Compared with men, women exhibit a longer QTc interval and an increased propensity toward torsade de pointes. In normal subjects, the QTc gender difference reflects QTc interval shortening in men during adolescence.

Methods: QTc intervals were analyzed according to age (< 16 or > or = 16 years) and gender in 460 genotyped blood relatives from families with long QT syndrome linked to chromosome 11p (KVLQT1; n = 199), 7q (HERG; n = 208) or 3p (SCN5A; n = 53).

Results: The mean QTc interval in genotype-negative blood relatives (n = 240) was shortest in men, but similar among women, boys and girls. For genotype-positive blood relatives, men exhibited the shortest mean QTc interval in chromosome 7q- and 11p-linked blood relatives (n = 194), but not in the smaller 3p-linked group (n = 26). Among pooled 7q- and 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) as significant predictors of the absolute QT interval. A shorter mean QT interval in men was most evident for heart rates < 60 beats/min.

Conclusions: In familial long QT syndrome linked to either chromosome 7q or 11p, men exhibit shorter mean QTc values than both women and children, for both genotype-positive and -negative blood relatives. Thus, adult gender differences in propensity toward torsade de pointes may reflect the relatively greater presence in men of a factor that blunts QT prolongation responses, especially at slow heart rates.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Child
  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 3
  • Chromosomes, Human, Pair 7
  • Electrocardiography
  • Female
  • Genetic Linkage
  • Genotype
  • Heart Rate / genetics
  • Heart Rate / physiology*
  • Humans
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / physiopathology
  • Male
  • Regression Analysis
  • Sex Factors
  • Torsades de Pointes / genetics