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Remdesivir therapy associated with Bradycardia in SARS-CoV2
Clinical Cardiology ( IF 2.4 ) Pub Date : 2021-07-28 , DOI: 10.1002/clc.23700
Sabina Kumar 1 , Christina Arcuri 1 , Sumanta Chaudhuri 1 , Rahul Gupta 1 , Mahendra Aseri 1 , Pranav Barve 1 , Shivang Shah 2, 3
Affiliation  

Thank you Barkas et al. for your interest in our article titled “A novel study on SARS-COV-2 virus associated bradycardia as a predictor of mortality-retrospective multicenter analysis.”1 In our large multicenter retrospective study, 28.7% of patients who received remdesivir developed an absolute bradycardic (HR <50) response during their hospitalization. Unfortunately, we could not comment if remdesivir was the sole cause of bradycardia because there was a high incidence of bradycardia in individuals who were not on remdesivir.

The possible mechanism for remdesivir causing bradycardia is still up for debate. The active metabolite is a nucleotide triphosphate which is a derivate similar to adenosine triphosphate (ATP).2 ATP has been shown to induce SA nodal automaticity through vagal simulation.3 In addition, ATP metabolite adenosine exerts negative chrontropic and dromotropic effects, which could affect AV nodal conduction.3

In the future, we agree with Barkas et al. that remdesivir and development of bradycardia needs to be investigated further. Touafchia et al. used the WHO safety report database reported a 31% incidence of bradycardia in those individuals receiving remdesivir. 75% of patients with bradycardia went on to develop serious complications including death.4 These results were very similar as seen in our study as well.

Barkas et al. bring up a good point on the relationship between onset of remdesivir exposure and development of bradycardia. Remdesivir has a high affinity to bind to viral polymerases; however, there is a chance for cross-reactivity with human mitochondrial RNA polymerase, which could lead to mitochonridal dysfunction and subsequent cardiomyocte toxicity. Choi et al. showed that the cytotoxic effects of remdesivir increased overtime (48 hours vs. 24 hours), in addition to reducing cell viability.5

Multiple case reports have also discussed remdesivir-causing bradycardia.5 Gubitosa et al. wrote a case report on a 54 y/o female who had marked sinus bradycardia (HR ~ 38 BPM) within 24 hours of receiving remdesivir.6 Sanchez-Codez and colleagues described a case report where a 13 year old male had a heart rate around 40 BPM after his third dose of remdesivir.7 Fralick et al. and team recently reported a patient who developed bradycardia (HR ~50 BPM) 48 hours after the administration.8 Through our literature review, we found more than 10 case reports discussing remdesivir administration and subsequent bradycardia. In most of the case reports, there was only a transient bradycardic event followed by normalization of heart rate after the discontinuation of the medication.

We are in the process of pursuing a retrospective analysis looking specifically at the timing of remdesivir and subsequent bradycardia. We invite anyone to send a message to the corresponding author if they want to collaborate on our study.



中文翻译:

瑞德西韦治疗与 SARS-CoV2 中的心动过缓有关

谢谢巴卡斯等人。感谢您对我们题为“关于 SARS-COV-2 病毒相关心动过缓作为死亡率回顾性多中心分析的预测因子的新研究”的文章感兴趣。1在我们的大型多中心回顾性研究中,28.7% 的接受瑞德西韦治疗的患者在住院期间出现了绝对心动过缓(HR <50)反应。不幸的是,我们无法评论瑞德西韦是否是心动过缓的唯一原因,因为在未服用瑞德西韦的个体中心动过缓的发生率很高。

瑞德西韦引起心动过缓的可能机制仍有争议。活性代谢物是核苷酸三磷酸,它是类似于三磷酸腺苷 (ATP) 的衍生物。2 ATP 已被证明可通过迷走神经模拟诱导 SA 节点自律性。3此外,ATP 代谢物腺苷具有负时变和变时效应,可能影响 AV 结传导。3

在未来,我们同意 Barkas 等人的观点。需要进一步研究瑞德西韦和心动过缓的发展。Touafchia 等人。使用 WHO 安全报告数据库报告,在接受瑞德西韦治疗的个体中,心动过缓的发生率为 31%。75% 的心动过缓患者继续出现包括死亡在内的严重并发症。4这些结果也与我们的研究中看到的非常相似。

巴卡斯等人。提出了一个很好的观点,即瑞德西韦暴露的发作与心动过缓的发展之间的关系。瑞德西韦与病毒聚合酶结合的亲和力很高;然而,有可能与人类线粒体 RNA 聚合酶发生交叉反应,这可能导致线粒体功能障碍和随后的心肌毒性。崔等人。表明瑞德西韦的细胞毒性作用会随着时间的推移而增加(48 小时对 24 小时),此外还会降低细胞活力。5

多个病例报告也讨论了瑞德西韦引起的心动过缓。5古比托萨等人。写了一篇关于一名 54 岁女性在接受瑞德西韦后 24 小时内出现明显的窦性心动过缓(HR ~ 38 BPM)的病例报告。6 Sanchez-Codez 及其同事描述了一个病例报告,一名 13 岁男性在第三剂瑞德西韦后心率约为 40 BPM。7 Fralick 等人。和团队最近报道了一名患者在给药 48 小时后出现心动过缓(HR ~50 BPM)。8通过我们的文献回顾,我们发现了 10 多份讨论瑞德西韦给药和随后的心动过缓的病例报告。在大多数病例报告中,仅出现一过性心动过缓事件,停药后心率正常。

我们正在进行一项回顾性分析,特别关注瑞德西韦的时间和随后的心动过缓。如果他们想在我们的研究中进行合作,我们邀请任何人向通讯作者发送消息。

更新日期:2021-09-09
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