Sex differences in long QT syndrome

Abstract

Long QT Syndrome (LQTS) is a rare, inherited channelopathy characterized by cardiac repolarization dysfunction, leading to a prolonged rate-corrected QT interval in patients who are at risk for malignant ventricular tachyarrhythmias, syncope, and even sudden cardiac death. A complex genetic origin, variable expressivity as well as incomplete penetrance make the diagnosis a clinical challenge. In the last 10 years, there has been a continuous improvement in diagnostic and personalized treatment options. Therefore, several factors such as sex, age diagnosis, QTc interval, and genetic background may contribute to risk stratification of patients, but it still currently remains as a main challenge in LQTS. It is widely accepted that sex is a risk factor itself for some arrhythmias. Female sex has been suggested as a risk factor in the development of malignant arrhythmias associated with LQTS. The existing differences between the sexes are only manifested after puberty, being the hormones the main inducers of arrhythmias. Despite the increased risk in females, no more than 10% of the available publications on LQTS include sex-related data concerning the risk of malignant arrhythmias in females. Therein, the relevance of our review data update concerning women and LQTS.

Keywords: arrhythmias; gender; long QT syndrome; sudden cardiac death; woman.

Figure 1

(A)- publications focused on long QT syndrome (pubMed, January 2023). From approximately 11,500 publications about Long QT Syndrome, less than 10% (800 publications) included any data concerning females/women or gender/sex differences. (B)- Time-line of publications focused on Long QT Syndrome and sex differences (PubMed, January 2023). Since 2005, the number of publications including any data concerning gender/sex differences has been maintained at nearly 45–50 studies per year.

Figure 2

Risk of malignant arrhythmias in women after the onset of adolescence. High risk situations are QTc more than 500msec, peripartum and post-partum periods, and deleterious variants in loop-pore of the KCNH2 gene. QTc: QT corrected; LQTS: Long QT Syndrome; LP/P: Likely Pathogenic/Pathogenic.