Division of Cardiology Clinical Cardiovascular Research Center University of Rochester Medical Center Rochester NY.
Departments of Cardiovascular Medicine (Division of Heart Rhythm Services), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology and the Windland Smith Rice Genetic Heart Rhythm Clinic), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory) Mayo Clinic Rochester MN.
J Am Heart Assoc. 2021 Jul 20;10(14):e021088. doi: 10.1161/JAHA.121.021088. Epub 2021 Jul 9.
Background We aimed to provide personalized risk estimates for cardiac events (CEs) and life-threatening events in women with either type 1 or type 2 long QT. Methods and Results The prognostic model was derived from the Rochester Long QT Syndrome Registry, comprising 767 women with type 1 long QT (n=404) and type 2 long QT (n=363) from age 15 through 60 years. The risk prediction model included the following variables: genotype/mutation location, QTc-specific thresholds, history of syncope, and β-blocker therapy. A model was developed with the end point of CEs (syncope, aborted cardiac arrest, or long QT syndrome-related sudden cardiac death), and was applied with the end point of life-threatening events (aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shocks). External validation was performed with data from the Mayo Clinic Genetic Heart Rhythm Clinic (N=467; type 1 long QT [n=286] and type 2 long QT [n=181]). The cumulative follow-up duration among the 767 enrolled women was 22 243 patient-years, during which 323 patients (42%) experienced ≥1 CE. Based on genotype-phenotype data, we identified 3 risk groups with 10-year projected rates of CEs ranging from 15%, 29%, to 51%. The corresponding 10-year projected rates of life-threatening events were 2%, 5%, and 14%. C statistics for the prediction model for the 2 respective end points were 0.68 (95% CI 0.65-0.71) and 0.71 (95% CI 0.66-0.76). Corresponding C statistics for the model in the external validation Mayo Clinic cohort were 0.65 (95% CI 0.60-0.70) and 0.77 (95% CI 0.70-0.84). Conclusions This is the first risk prediction model that provides absolute risk estimates for CEs and life-threatening events in women with type 1 or type 2 long QT based on personalized genotype-phenotype data. The projected risk estimates can be used to guide female-specific management in long QT syndrome.
背景 我们旨在为 1 型或 2 型长 QT 女性提供心脏事件 (CE) 和危及生命事件的个性化风险估计。
方法和结果 该预后模型源自罗切斯特长 QT 综合征登记处，包括 767 名年龄在 15 至 60 岁的 1 型长 QT (n=404) 和 2 型长 QT (n=363) 女性。风险预测模型包括以下变量：基因型/突变位置、QTc 特异性阈值、晕厥史和β受体阻滞剂治疗。建立了一个以 CEs（晕厥、心搏骤停或长 QT 综合征相关心源性猝死）为终点的模型，并将其应用于危及生命事件（心搏骤停、心源性猝死或适当的除颤电击）的终点。利用梅奥诊所遗传心律失常诊所的数据进行外部验证 (N=467；1 型长 QT [n=286] 和 2 型长 QT [n=181])。767 名入组女性的累积随访时间为 22243 患者年，在此期间 323 名患者 (42%) 经历了≥1 次 CE。根据基因型表型数据，我们确定了 3 个风险组，10 年预计 CE 发生率分别为 15%、29%和 51%。相应的 10 年预计危及生命事件发生率分别为 2%、5%和 14%。预测模型对于这两个终点的 C 统计量分别为 0.68(95%CI 0.65-0.71)和 0.71(95%CI 0.66-0.76)。在外部验证的梅奥诊所队列中，模型的相应 C 统计量分别为 0.65(95%CI 0.60-0.70)和 0.77(95%CI 0.70-0.84)。
结论 这是第一个基于个性化基因型表型数据，为 1 型或 2 型长 QT 女性提供心脏事件和危及生命事件的绝对风险估计的风险预测模型。预测风险估计可用于指导长 QT 综合征的女性特异性管理。
