Referenced in: none

Automatically associated channels: Kir6.2 , Kv11.1 , Kv7.1

Title: Mutation and gender-specific risk in type 2 long QT syndrome: implications for risk stratification for life-threatening cardiac events in patients with long QT syndrome.

Authors: Dimitry Migdalovich, Arthur J Moss, Coeli M Lopes, Jason Costa, Gregory Ouellet, Alon Barsheshet, 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, 2011 Oct , 8, 1537-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21440677

Abstract
Men and women with type 2 long QT syndrome (LQT2) exhibit time-dependent differences in the risk for cardiac events. We hypothesized that data regarding the location of the disease-causing mutation in the KCNH2 channel may affect gender-specific risk in LQT2.This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information.The risk for life-threatening cardiac events from birth through age 40 years (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) was assessed among 1,166 LQT2 male (n = 490) and female (n = 676) patients by the location of the LQTS-causing mutation in the KCNH2 channel (prespecified in the primary analysis as pore-loop vs. non-pore-loop).During follow-up, the cumulative probability of life-threatening cardiac events years was significantly higher among LQT2 women (26%) as compared with men (14%; P <.001). Multivariate analysis showed that the risk for life-threatening cardiac events was not significantly different between women with and without pore-loop mutations (hazard ratio 1.20; P =.33). In contrast, men with pore-loop mutations displayed a significant >2-fold higher risk of a first ACA or SCD as compared with those with non-pore-loop mutations (hazard ratio 2.18; P = .01). Consistently, women experienced a high rate of life-threatening events regardless of mutation location (pore-loop: 35%, non-pore-loop: 23%), whereas in men the rate of ACA or SCD was high among those with pore-loop mutations (28%) and relatively low among those with non-pore-loop mutations (8%).Combined assessment of clinical and mutation-specific data can be used for improved risk stratification for life-threatening cardiac events in LQT2.