Department of Medicine, University of California, San Francisco.
Department of Epidemiology and Biostatistics, University of California, San Francisco.
JAMA Intern Med. 2020 May 1;180(5):698-706. doi: 10.1001/jamainternmed.2020.0148.
QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown.
To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death.
DESIGN, SETTING, AND PARTICIPANTS: This prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019.
QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high).
Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause.
A total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P < .001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P = .04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P = .01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P = .02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P = .02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P = .001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group.
These findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.
当使用共识标准定义 QT 延长药物 (QTPM) 为导致心源性猝死 (SCD) 的危险因素时，这些药物被认为存在心律失常的原因。但是 QTPM 对尸检定义的心律失常性猝死 (SAD) 的影响尚不清楚。
评估 QTPM 与尸检定义的 SAD 与非心律失常性猝死之间的关联。
设计、地点和参与者：这项前瞻性全县病例对照研究纳入了作为旧金山死后系统调查心源性猝死研究 (POST SCD) 的一部分进行尸检的世界卫生组织定义的 (假定) SCD 病例，以确定心律失常或非心律失常的原因，以及加利福尼亚州旧金山县因创伤而死亡的病例（以下简称创伤对照组）。从 2011 年 2 月 1 日至 2014 年 3 月 1 日。使用多元回归评估 QTPM 与假定 SCD、尸检定义的 SAD 和非 SAD 与创伤对照组的风险关联。通过处方清单和死后毒理学发现来确定药物暴露情况，并用 QTPM 暴露评分（范围 0-20）来计算总和。数据于 2018 年 9 月 1 日至 2019 年 6 月 15 日进行分析。
通过 QTPM 评分（1 表示低；2-4 表示中度；>4 表示高）来衡量 QTPM 暴露情况。
因创伤、假定 SCD 以及无尸检发现的非心律失常性猝死和 SAD 而导致的死亡。
共纳入 629 名患者（平均[标准差]年龄为 61.4[15.7]岁；439 名男性[69.8%]），525 名患有假定 SCD 和 104 名创伤性死亡对照组。与创伤对照组相比，假定 SCD 患者的暴露程度更高，更有可能服用任何 QTPM（291[55.4%]与 28[26.9%]；P<0.001）。使用 QTPM 与假定 SCD 的低（比值比 [OR]，2.25[95%置信区间，1.03-4.96]；P=0.04）和高（OR，6.70[95%置信区间，1.47-30.67]；P=0.01）暴露组的风险增加相关。在尸检裁决后，使用 QTPM 与非心律失常性猝死的风险增加相关（低风险 OR，2.88[95%置信区间，1.18-6.99；P=0.02]；中风险 OR，2.62[95%置信区间，1.20-5.73；P=0.02]；高风险 OR，14.22[95%置信区间，2.91-69.30；P=0.001]），但在所有暴露组中均未与 SAD 相关。排除最高暴露组中隐匿性过量非心律失常性猝死病例后，这种关联减弱。
这些发现证实了 QTPM 与假定 SCD 之间的关联；然而，尸检后，这种风险是与非心律失常性猝死的特定原因相关的。使用共识 SCD 标准的研究可能高估了 QTPM 与 SAD 风险的关联。
