Peter J.Sdwartz教授(图1)是意大利米兰IRCCS(科研、住院及医疗保健研究所)心律失常中心和心血管遗传学实验室的主任。他是最早进行长QT综合征(LQTS)和心脏性猝死(SCD)相关性研究的学者。在近50年的时间里,他在这一研究领域进行了开创...Peter J.Sdwartz教授(图1)是意大利米兰IRCCS(科研、住院及医疗保健研究所)心律失常中心和心血管遗传学实验室的主任。他是最早进行长QT综合征(LQTS)和心脏性猝死(SCD)相关性研究的学者。在近50年的时间里,他在这一研究领域进行了开创性的工作,包括LQTS的诊断和治疗及其相关基础研究,建立全球LQTS注册中心阐明左心交感神经切除术的基本原理等。近年,他还提出了修饰基因的重要作用,进而为基因特异性治疗开辟了道路。2021年3月,Schwartz教授在《Europe Heart Journal》发表题为"长QT综合征研究50年:从一无所知到精准诊疗(1970-2020)"的文章,介绍了他从最初到现阶段参与的LQTS研究工作重点回顾了LQTS发现早期一些鲜为人知的历程,并发表了一些珍贵的历史资料。本文对上述情况加以简要介绍。展开更多
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.
