Combined assessment of sex- and mutation-specific information for risk stratification in type 1 long QT syndrome.

Abstract

BACKGROUND:

Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events.

OBJECTIVE:

We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene.

METHODS:

The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1051 individuals with LQT1 (450 men and 601 women) by the location and function of the LQT1-causing mutation (prespecified as mutations in the intracellular domains linking the membrane-spanning segments [ie, S2-S3 and S4-S5 cytoplasmic loops] involved in adrenergic channel regulation vs other mutations).

RESULTS:

Multivariate analysis showed that during childhood (age group: 0-13 years) men had >2-fold (P < .003) increased risk for ACA/SCD than did women, whereas after the onset of adolescence the risk for ACA/SCD was similar between men and women (hazard ratio = 0.89 [P = .64]). The presence of cytoplasmic-loop mutations was associated with a 2.7-fold (P < .001) increased risk for ACA/SCD among women, but it did not affect the risk among men (hazard ratio 1.37; P = .26). Time-dependent syncope was associated with a more pronounced risk-increase among men than among women (hazard ratio 4.73 [P < .001] and 2.43 [P = .02], respectively), whereas a prolonged corrected QT interval (≥ 500 ms) was associated with a higher risk among women than among men.

CONCLUSION:

Our findings suggest that the combined assessment of clinical and mutation location/functional data can be used to identify sex-specific risk factors for life-threatening events for patients with LQT1.

• Authors: Jason Costa, Coeli M Lopes, Alon Barsheshet, Arthur J Moss, Dmitriy Migdalovich, Gregory Ouellet, Scott McNitt, Slava Polonsky, Jennifer L Robinson, Wojciech Zareba, Michael J Ackerman, Jesaia Benhorin, Elizabeth S Kaufman, Pyotr G Platonov, Wataru Shimizu, Jeffrey A Towbin, G Michael Vincent, Arthur A M Wilde, Ilan Goldenberg
• Journal: Heart rhythm (Heart Rhythm) Vol. 9 Issue 6 Pg. 892-8 (Jun 2012) ISSN: 1556-3871 [Electronic] United States
• PMID: 22293141 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• KCNQ1 Potassium Channel
• DNA

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• DNA (genetics)
• Death, Sudden, Cardiac (epidemiology, etiology)
• Electrocardiography
• Female
• Genotype
• Global Health
• Humans
• Incidence
• Infant
• Infant, Newborn
• KCNQ1 Potassium Channel (genetics, metabolism)
• Male
• Mutation
• Risk Assessment (methods)
• Risk Factors
• Romano-Ward Syndrome (complications, epidemiology, genetics)
• Sex Distribution
• Sex Factors
• Survival Rate (trends)
• Young Adult