Referenced in: none

Automatically associated channels: Kir6.2 , Kv7.1

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

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, date & volume: Heart Rhythm, 2012 Jun , 9, 892-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22293141

Abstract
Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events.We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene.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).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.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.