Objectives We sought to compare the arrhythmic risk and sensitivity to sympath etic stimulation of mutations located in transmembrane regions and C-terminal r egions of the KCNQ1 channel in the LQT1 form of congenital...Objectives We sought to compare the arrhythmic risk and sensitivity to sympath etic stimulation of mutations located in transmembrane regions and C-terminal r egions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome(LQTS ). Background The LQT1 syndrome is frequently manifested with variable expressiv ity and incomplete penetrance and is much more sensitive to sympathetic stimulat ion 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-term inal mutations were enrolled from five Japanese institutes. Results Patients wit h transmembrane mutations were more frequently affected based on electrocardiogr aphic (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 dea th: 15%vs. 0%, p=0.03) than those with C-terminal mutations. Patients with tr ansmembrane 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 ris k per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, includi ng Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in pa tients with transmembrane mutations than in those with C-terminal mutations (p< 0.005) . Moreover, the corrected Q-Tend and Tpeak-end were more prominently i ncreased with exercise in patients with transmembrane mutations (p< 0.005). Conc lusions In this multicenter Japanese population, LQT1 patients with transmembran e mutations are at higher risk of congenital LQTS-related cardiac events and ha ve greater sensitivity to sympathetic stimulation, as compared with patients wit h C-terminal mutations.展开更多
文摘Objectives We sought to compare the arrhythmic risk and sensitivity to sympath etic stimulation of mutations located in transmembrane regions and C-terminal r egions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome(LQTS ). Background The LQT1 syndrome is frequently manifested with variable expressiv ity and incomplete penetrance and is much more sensitive to sympathetic stimulat ion 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-term inal mutations were enrolled from five Japanese institutes. Results Patients wit h transmembrane mutations were more frequently affected based on electrocardiogr aphic (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 dea th: 15%vs. 0%, p=0.03) than those with C-terminal mutations. Patients with tr ansmembrane 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 ris k per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, includi ng Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in pa tients with transmembrane mutations than in those with C-terminal mutations (p< 0.005) . Moreover, the corrected Q-Tend and Tpeak-end were more prominently i ncreased with exercise in patients with transmembrane mutations (p< 0.005). Conc lusions In this multicenter Japanese population, LQT1 patients with transmembran e mutations are at higher risk of congenital LQTS-related cardiac events and ha ve greater sensitivity to sympathetic stimulation, as compared with patients wit h C-terminal mutations.
