Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette and Indianapolis, Indiana, United States of America.
Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana, United States of America.
PLoS One. 2024 Aug 19;19(8):e0308999. doi: 10.1371/journal.pone.0308999. eCollection 2024.
Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced QT interval prolongation. It is unknown if HF with preserved ejection fraction (HFpEF) is also associated with an increased risk. Dofetilide and sotalol are potent QT interval-prolonging agents that are frequently used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity. We tested the hypothesis that the risk of QT interval prolongation associated with dofetilide and sotalol is increased in patients with HFpEF. We conducted a retrospective cohort study conducted using electronic health records from the Indiana Network for Patient Care (January 31, 2010 -May 3, 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, and absence of QT interval records, we identified patients taking dofetilide or sotalol among three groups: HFrEF (n = 138), HFpEF (n = 109), and no HF (n = 729). QT prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) for QT prolongation were determined by univariate analysis. Adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates. QTc prolongation associated with dofetilide or sotalol occurred in 53.2%, 71.7% and 30.0% of patients with HFpEF, HFrEF, and patients with no HF, respectively. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of QTc prolongation were significantly higher in patients with HFpEF [OR = 1.98 (95% CI 1.17-3.33)], and in those with HFrEF [OR = 5.23, (3.15-8.67)], compared to those with no evidence of HF. The odds of QT prolongation among inpatients receiving dofetilide or sotalol were increased in patients with HFpEF and HFrEF compared to those who did not have HF.
射血分数降低的心力衰竭（HFrEF）是药物引起 QT 间期延长的危险因素。目前尚不清楚射血分数保留的心力衰竭（HFpEF）是否也与风险增加有关。多非利特和索他洛尔是两种强效的 QT 间期延长药物，常用于 HFpEF 患者，而心房颤动是 HFpEF 的常见合并症。我们检验了假设，即 HFpEF 患者使用多非利特和索他洛尔与 QT 间期延长相关的风险增加。我们进行了一项回顾性队列研究，该研究使用了印第安纳州患者护理网络（2010 年 1 月 31 日至 2021 年 5 月 3 日）的电子健康记录。在去除 HFpEF 和 HFrEF 重叠诊断、无诊断代码和无 QT 间期记录的患者后，我们在三组患者中确定了使用多非利特或索他洛尔的患者：HFrEF（n = 138）、HFpEF（n = 109）和无 HF（n = 729）。QT 延长定义为多非利特/索他洛尔治疗期间心率校正 QT（QTc）>500 ms。通过单变量分析确定 QT 延长的未调整比值比（OR）。通过广义估计方程（GEE）与对数链接确定调整后的 OR，以考虑个体的住院时间和协变量的不同集群。HFpEF、HFrEF 和无 HF 患者中，多非利特或索他洛尔相关的 QTc 延长分别发生在 53.2%、71.7%和 30.0%的患者中。在校正年龄、性别、种族、血清钾和镁浓度、肾功能、合并药物治疗和合并症后，HFpEF [OR = 1.98（95%CI 1.17-3.33）]和 HFrEF [OR = 5.23，（3.15-8.67）]患者 QTc 延长的调整比值明显高于无 HF 患者。与无 HF 患者相比，HFpEF 和 HFrEF 住院患者接受多非利特或索他洛尔治疗时，QT 延长的几率增加。
