Supplementary Material for: Hydroxychloroquine Inhibits Cardiac Conduction in Aged Patients with Nonmalaria Diseases

<b><i>Background:</i></b> The COVID-19 pandemic has brought increased focus on hydroxychloroquine (HCQ), as doctors, the medical community, and policymakers around the world attempt to understand how the risks of HCQ weigh against unknown benefits. We aim to evaluate the effects of HCQ on cardiac conduction, thus contributing to the global understanding of implications of HCQ use. <b><i>Methods:</i></b> We reviewed 717 cases of nonmalaria patients treated with HCQ (302) or without HCQ (415) in our hospital from 2008 to 2019, analyzed the cardiac conduction recorded by electrocardiogram (122 vs. 180) including heart rate (HR), PR, and corrected-QT (QTc) intervals, and explored the relationship of cardiac conduction with age, HCQ dosage, HCQ duration, sex, and primary diseases in HCQ users. <b><i>Results:</i></b> The all-cause mortality is similar between HCQ and non-HCQ groups (4.0 vs. 4.3%, <i>p</i> = 0.85). Patients aged 45 years or older, not younger ones, have lower HR (80.1 ± 1.7 vs. 85.7 ± 1.8 bpm, <i>p</i> = 0.03) but longer PR (163 ± 3.4 vs. 146.6 ± 4.2 ms, <i>p</i> = 0.003) and QTc (417.8 ± 3.8 vs. 407.7 ± 2.7 ms, <i>p</i> = 0.03) in HCQ than those in non-HCQ. The age in the HCQ group is positively correlated with PR (<i>R</i> = 0.31, <i>p</i> &lt; 0.01) and QTc (<i>R</i> = 0.34, <i>p</i> &lt; 0.01) but not HR. HR, PR, and QTc are not related to HCQ dosage (0.1–0.6 g/day), HCQ duration (0.2–126 months), sex, primary diseases, and repeated exams. <b><i>Conclusion:</i></b> Age is the most important risk factor of HCQ on cardiac conduction in nonmalaria patients. Electrocardiogram monitoring is suggested in aged patients due to the effects of HCQ on HR, PR, and QTc.

**研究背景：** 新型冠状病毒肺炎（COVID-19）大流行使得羟氯喹（hydroxychloroquine, HCQ）受到更多关注，全球范围内的医师、医学界及政策制定者均试图厘清羟氯喹的风险与其尚不明确的获益之间的权衡关系。本研究旨在评估羟氯喹对心脏传导的影响，以期为全球范围内理解羟氯喹使用的相关影响提供依据。
**研究方法：** 本研究回顾性分析了2008年至2019年本院收治的717例非疟疾患者的病例资料，其中接受羟氯喹治疗者302例，未接受者415例。对两组经心电图（electrocardiogram）记录的心脏传导指标进行分析，其中羟氯喹组122例，非羟氯喹组180例，指标包括心率（heart rate, HR）、PR间期及校正QT间期（corrected-QT, QTc）；同时探讨了羟氯喹使用者的心脏传导指标与年龄、羟氯喹给药剂量、用药时长、性别及基础疾病之间的关联。
**研究结果：** 羟氯喹组与非羟氯喹组的全因死亡率无显著差异（4.0% vs 4.3%，p=0.85）。在45岁及以上的患者中，羟氯喹组的心率（80.1±1.7 vs 85.7±1.8 次/分钟，p=0.03）低于非羟氯喹组，但其PR间期（163±3.4 vs 146.6±4.2 ms，p=0.003）及QTc间期（417.8±3.8 vs 407.7±2.7 ms，p=0.03）均长于非羟氯喹组；45岁以下患者未观察到此类差异。羟氯喹组患者的年龄与PR间期（R=0.31，p<0.01）及QTc间期（R=0.34，p<0.01）呈正相关，但与心率无显著关联。心率、PR间期及QTc间期与羟氯喹给药剂量（0.1~0.6 g/天）、用药时长（0.2~126个月）、性别、基础疾病及重复检查均无显著关联。
**研究结论：** 在非疟疾患者中，年龄是羟氯喹影响心脏传导的最主要危险因素。鉴于羟氯喹对心率、PR间期及QTc间期的影响，建议对老年患者开展心电图监测。