Sex hormones and repolarization dynamics during the menstrual cycle in women with congenital long QT syndrome

Milica Bjelic, Wojciech Zareba, Derick R. Peterson, Arwa Younis, Mehmet K. Aktas, David T. Huang, Spencer Rosero, Kris Cutter, Scott McNitt, Xiaojuan Xia, Bonnie D. MacKecknie, Rebecca Horn, Nona Sotoodehnia, Peter J. Kudenchuk, Thomas D. Rea, Dan E. Arking, Arthur A.M. Wilde, Wataru Shimizu, Michael J. Ackerman, Ilan Goldenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Women with congenital long QT syndrome (LQTS) experience increased cardiac event risk after the onset of adolescence, perhaps stemming from the known modulating effects of sex hormones on the cardiac potassium channels. Objective: We hypothesized that the effect of sex hormones on cardiac ion channel function may modify electrocardiographic (ECG) parameters associated with the propensity for ventricular tachyarrhythmias during the menstrual cycle in women with LQTS. Methods: We prospectively enrolled 65 women with congenital LQTS (type 1 LQTS [LQT1], n = 24 [36.9%]; type 2 LQTS [LQT2], n = 20 [30.8%]) and unaffected female relatives (n = 21 [32.3%]). Patients underwent three 7-day ECG recordings during their menstrual cycles. Simultaneous saliva testing of sex hormone levels was conducted on the first day of each 7-day ECG recording cycle. Results: The mean age was 35 ± 8 years, without a significant difference among the groups. In women with LQT2, linear mixed effects models showed significant inverse correlations of the corrected QT interval with progesterone levels (P < .001) and with the progesterone to estradiol ratio (P < .001). Inverse relationships of the R-R interval with estradiol levels (P = .003) and of the T-wave duration with testosterone levels (P = .014) were also observed in women with LQT2. In contrast, no significant associations were observed between ECG parameters and sex hormone levels in women with LQT1 or unaffected relatives. Conclusion: This is the first study to prospectively assess correlations between repolarization dynamics and sex hormone levels during the menstrual cycle in women with congenital LQTS. Our findings show genotype-specific unique corrected QT dynamics during the menstrual cycle that may affect the propensity for ventricular tachyarrhythmia in women with LQTS, particularly women with LQT2.

Original languageEnglish (US)
JournalHeart rhythm
DOIs
StateAccepted/In press - 2022

Keywords

  • ECG parameters
  • Long QT syndrome
  • LQT2
  • QT
  • Sex hormones
  • Women

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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