Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; Universidad Miguel Hernández de Elche, Alicante, Spain.
Internal Medicine and Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain.
Int J Antimicrob Agents. 2020 Oct;56(4):106142. doi: 10.1016/j.ijantimicag.2020.106142. Epub 2020 Aug 24.
This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.
本纵向前瞻性队列研究旨在评估 COVID-19 患者接受包含羟氯喹（HCQ）的联合治疗时发生 QTc 间期延长的风险及其预测因素。治疗期间出现中度至重度 QTc 延长定义为男性 QTc 间期＞470ms 或女性＞480ms。患者在严格的心脏监护下接受治疗。共纳入 105 例成年人[56%为男性；中位（IQR）年龄 69（57-79）岁]。所有患者均接受 HCQ 联合阿奇霉素（AZM）治疗，95 例（90%）还接受洛匹那韦/利托那韦（LPV/r）治疗。同时使用被归类为有发生尖端扭转型室性心动过速（TdP）风险的伴随药物的患者有 81 例（77%）。14 例（13%）患者出现中度至重度 QTc 延长，主要发生在基线后第 3-5 天，其中 6 例（6%）发生严重延长（＞500ms）。无 TdP 心律失常或 TdP 相关死亡证据。HCQ+AZM 中添加 LPV/r 并未显著延长 QTc 间期。多变量 Cox 回归显示，具有已知 TdP 风险的合并用药（HR=11.28，95%CI 1.08-117.41）、较高的中性粒细胞与淋巴细胞比值（HR=1.10，95%CI 每单位增加 1.03-1.18）和较高的血清高敏心肌肌钙蛋白 I（HR=4.09，95%CI 每单位增加 1.36-12.2）是导致中度至重度 QTc 延长的主要因素。在这个经过严密筛选和监测的队列中，在 COVID-19 患者接受包含 HCQ 的药物治疗期间，未观察到与 QTc 延长相关的并发症。心肌损伤伴有肌钙蛋白升高和强烈炎症反应的证据，特别是更高的 NLR，是需要仔细监测 QTc 间期的情况。
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