Advanced

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

Migdalovich, Dimitry; Moss, Arthur J.; Lopes, Coeli M.; Costa, Jason; Ouellet, Gregory; Barsheshet, Alon; McNitt, Scott; Polonsky, Slava; Robinson, Jennifer L. and Zareba, Wojciech, et al. (2011) In Heart Rhythm 8(10). p.1537-1543
Abstract
BACKGROUND 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. OBJECTIVE This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information. METHODS 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... (More)
BACKGROUND 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. OBJECTIVE This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information. METHODS 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). RESULTS 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%, nonpore-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%). CONCLUSION Combined assessment of clinical and mutation-specific data can be used for improved risk stratification for life-threatening cardiac events in LQT2. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Long QT syndrome, Pore-loop mutations, Sudden cardiac death, Gender
in
Heart Rhythm
volume
8
issue
10
pages
1537 - 1543
publisher
Elsevier
external identifiers
  • wos:000295595200007
  • scopus:80053051796
ISSN
1547-5271
DOI
10.1016/j.hrthm.2011.03.049
language
English
LU publication?
yes
id
f1652dd8-1c40-4216-b30c-bd8e22133b71 (old id 2212769)
date added to LUP
2011-12-01 08:34:22
date last changed
2017-07-23 03:09:14
@article{f1652dd8-1c40-4216-b30c-bd8e22133b71,
  abstract     = {BACKGROUND 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. OBJECTIVE This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information. METHODS 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). RESULTS 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 &lt;.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 &gt; 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%, nonpore-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%). CONCLUSION Combined assessment of clinical and mutation-specific data can be used for improved risk stratification for life-threatening cardiac events in LQT2.},
  author       = {Migdalovich, Dimitry and Moss, Arthur J. and Lopes, Coeli M. and Costa, Jason and Ouellet, Gregory and Barsheshet, Alon and McNitt, Scott and Polonsky, Slava and Robinson, Jennifer L. and Zareba, Wojciech and Ackerman, Michael J. and Benhorin, Jesaia and Kaufman, Elizabeth S. and Platonov, Pyotr and Shimizu, Wataru and Towbin, Jeffrey A. and Vincent, G. Michael and Wilde, Arthur A. M. and Goldenberg, Ilan},
  issn         = {1547-5271},
  keyword      = {Long QT syndrome,Pore-loop mutations,Sudden cardiac death,Gender},
  language     = {eng},
  number       = {10},
  pages        = {1537--1543},
  publisher    = {Elsevier},
  series       = {Heart Rhythm},
  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},
  url          = {http://dx.doi.org/10.1016/j.hrthm.2011.03.049},
  volume       = {8},
  year         = {2011},
}