Abstract
Objectives We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS). Background The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms. Methods Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes. Results Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p <0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p <0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p <0.005). Conclusions In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations.
| Original language | English |
|---|---|
| Pages (from-to) | 117-125 |
| Number of pages | 9 |
| Journal | Journal of the American College of Cardiology |
| Volume | 44 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 7 2004 |
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Keywords
- action potential duration
- APD
- Ca -activated chloride current
- deoxyribonucleic acid
- DNA
- fast component of the delayed rectifier potassium current
- I
- I
- I
ASJC Scopus subject areas
- Nursing(all)
Cite this
Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome : Multicenter study in Japan. / Shimizu, Wataru; Horie, Minoru; Ohno, Seiko; Takenaka, Kotoe; Yamaguchi, Masato; Shimizu, Masami; Washizuka, Takashi; Aizawa, Yoshifusa; Nakamura, Kazufumi; Ohe, Tohru; Aiba, Takeshi; Miyamoto, Yoshihiro; Yoshimasa, Yasunao; Towbin, Jeffrey A.; Priori, Silvia G.; Kamakura, Shiro.
In: Journal of the American College of Cardiology, Vol. 44, No. 1, 07.07.2004, p. 117-125.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome
T2 - Multicenter study in Japan
AU - Shimizu, Wataru
AU - Horie, Minoru
AU - Ohno, Seiko
AU - Takenaka, Kotoe
AU - Yamaguchi, Masato
AU - Shimizu, Masami
AU - Washizuka, Takashi
AU - Aizawa, Yoshifusa
AU - Nakamura, Kazufumi
AU - Ohe, Tohru
AU - Aiba, Takeshi
AU - Miyamoto, Yoshihiro
AU - Yoshimasa, Yasunao
AU - Towbin, Jeffrey A.
AU - Priori, Silvia G.
AU - Kamakura, Shiro
PY - 2004/7/7
Y1 - 2004/7/7
N2 - Objectives We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS). Background The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms. Methods Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes. Results Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p <0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p <0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p <0.005). Conclusions In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations.
AB - Objectives We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS). Background The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms. Methods Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes. Results Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p <0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p <0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p <0.005). Conclusions In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations.
KW - action potential duration
KW - APD
KW - Ca -activated chloride current
KW - deoxyribonucleic acid
KW - DNA
KW - fast component of the delayed rectifier potassium current
KW - I
KW - I
KW - I
UR - http://www.scopus.com/inward/record.url?scp=3242752714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3242752714&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2004.03.043
DO - 10.1016/j.jacc.2004.03.043
M3 - Article
VL - 44
SP - 117
EP - 125
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 1
ER -