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

被引:85
作者
Migdalovich, Dimitry
Moss, Arthur J.
Lopes, Coeli M. [2 ]
Costa, Jason
Ouellet, Gregory
Barsheshet, Alon
McNitt, Scott
Polonsky, Slava
Robinson, Jennifer L.
Zareba, Wojciech
Ackerman, Michael J. [3 ]
Benhorin, Jesaia [4 ]
Kaufman, Elizabeth S. [5 ]
Platonov, Pyotr G. [6 ]
Shimizu, Wataru [7 ]
Towbin, Jeffrey A. [8 ]
Vincent, G. Michael [9 ]
Wilde, Arthur A. M. [10 ]
Goldenberg, Ilan [1 ]
机构
[1] Univ Rochester, Med Ctr, Heart Res Follow Program, Div Cardiol, Rochester, NY 14642 USA
[2] Univ Rochester, Sch Med & Dent, Cardiovasc Res Inst, Rochester, NY 14642 USA
[3] Mayo Clin, Dept Pediat, Div Pediat Cardiol, Rochester, MN USA
[4] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Cardiol, IL-69978 Tel Aviv, Israel
[5] Case Western Reserve Univ, Heart & Vasc Res Ctr, Cleveland, OH 44106 USA
[6] Lund Univ, Dept Cardiol, Lund, Sweden
[7] Natl Cardiovasc Ctr, Div Cardiol, Dept Internal Med, Suita, Osaka 565, Japan
[8] Univ Cincinnati, Childrens Hosp, Dept Pediat, Cincinnati, OH USA
[9] LDS Hosp, Salt Lake City, UT USA
[10] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
基金
美国国家卫生研究院;
关键词
Long QT syndrome; Pore-loop mutations; Sudden cardiac death; Gender; HERG; REPOLARIZATION; CHANNELS;
D O I
10.1016/j.hrthm.2011.03.049
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1537 / 1543
页数:7
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