Cardiology Division of Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
J Am Coll Cardiol. 2011 Jan 4;57(1):51-9. doi: 10.1016/j.jacc.2010.07.038.
This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals.
Current data regarding the outcome of patients with concealed LQTS are limited.
Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤ 440 ms [n = 469]), LQTS with prolonged QTc interval (> 440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤ 440 ms [n = 1,525]).
The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age > 13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002).
Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.
本研究旨在评估长 QT 综合征（LQTS）患者 QT 间期正常（QTc≤440ms）患者的临床病程，并确定其发生威胁生命事件的风险因素。
目前有关隐匿性 LQTS 患者结局的数据有限。
通过 7 个跨国 LQTS 登记处的 3386 名基因分型患者，对 0 至 40 岁发生心脏性猝死（SCD）或心搏骤停（ACA）的临床和遗传风险因素进行评估，根据 QTc 间期分为 LQTS 伴正常 QTc 间期（≤440ms，n=469）、LQTS 伴长 QTc 间期（>440ms，n=1392）和无家族史（基因分型阴性，≤440ms，n=1525）。
伴正常 QTc 间期的 LQTS 患者发生 ACA 或 SCD 的累积概率（4%）明显低于伴长 QTc 间期的患者（15%）（p<0.001），但高于无家族史的患者（0.4%）（p<0.001）。伴正常 QTc 间期的 LQTS 患者发生 ACA 或 SCD 的危险因素包括突变特征（跨膜错义突变与非跨膜或非错义突变：风险比 6.32；p=0.006）和 LQTS 基因型（LQTS 1 型：LQTS 2 型，风险比 9.88；p=0.03；LQTS 3 型：LQTS 2 型，风险比 8.04；p=0.07），而临床因素（包括性别和 QTc 持续时间）仅与伴长 QTc 间期的患者发生 ACA 或 SCD 的风险显著增加相关（女性年龄>13 岁，风险比 1.90；p=0.002；QTc 持续时间每增加 10ms，风险增加 8%；p=0.002）。
基因确诊的隐匿性 LQTS 患者占高危 LQTS 人群的 25%左右。基因型数据，包括突变特征和 LQTS 基因型的信息，确定了这一总体风险较低的 LQTS 亚组发生 ACA 或 SCD 的风险增加。
