Tagle-Cornell Maria Cecilia, Ayoub Chadi, Bird Christen, Pereyra Milagros, Kenyon Courtney, Kamel Moaz, Iyengar Shruti, Vemulapalli Hema, Galasso Francesca, Girardo Marlene, Molly Klanderman, Srivathsan Komandoor
Department of Cardiovascular Disease, Mayo Clinic, Phoenix, AZ, USA.
Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Scottsdale, AZ, USA.
Int J Cardiol Heart Vasc. 2024 Aug 6;54:101475. doi: 10.1016/j.ijcha.2024.101475. eCollection 2024 Oct.
Atrial fibrillation is the most prevalent cardiac arrhythmia, presenting symptomatic patients with diminished quality of life and worsening of heart failure. Dofetilide, a class 3 antiarrhythmic agent, is a proven and safe rhythm control medication. Initial risk of QT prolongation leading to torsade de pointes (TdP) necessitates a standard protocol mandating hospitalization for three days for initiation.
To assess safety when adhering to initiation protocol and identify traits for susceptibility to TdP in elective dofetilide admissions.
We conducted a retrospective study involving patients admitted to Mayo Clinic sites across four states for elective inpatient initiation of dofetilide between 2003 and 2022. Patients' charts underwent review, focusing on dofetilide-related TdP occurrences, baseline characteristics including QT intervals, laboratory values, comorbidities, and concomitant medications. Patients who experienced TdP were subjected to further evaluation to identify potential risk factors.
Of 2036 patients identified, mean age 66.4 ± 11.4 years, and 67.2 % male, 16 experienced dofetilide-related TdP (incidence rate 0.79%). Notably, 81% (13/16) of TdP cases occurred in patients who deviated from the FDA/manufacturer algorithm protocol. The concomitant use of active intravenous diuretic therapy, digoxin, and QT-prolonging drugs emerged as identifiable risk factors. Additionally, females exhibited a higher incidence of TdP (1.5%) than males (0.44%) {odd ratio [OR] 3.46; P = 0.017}.
Overall incidence of TdP related to dofetilide initiation was low (0.79%). Adherence to protocol during elective hospital admissions appears extraordinarily safe. Patients who did not require concurrent use of intravenous diuretics, digoxin, or QT prolonging drugs exhibited lower risk of TdP.
心房颤动是最常见的心律失常，会使有症状的患者生活质量下降，心力衰竭病情恶化。多非利特是一种Ⅲ类抗心律失常药物，是一种经证实的安全的节律控制药物。初始时因QT间期延长导致尖端扭转型室速（TdP）的风险使得必须有一个标准方案，要求开始用药时需住院三天。
评估遵守起始方案时的安全性，并确定择期使用多非利特入院患者发生TdP的易患特征。
我们进行了一项回顾性研究，纳入2003年至2022年间在四个州的梅奥诊所各院区择期住院开始使用多非利特的患者。对患者病历进行审查，重点关注与多非利特相关的TdP发生情况、包括QT间期在内的基线特征、实验室检查值、合并症和伴随用药情况。对发生TdP的患者进行进一步评估以确定潜在危险因素。
在确定的2036例患者中，平均年龄66.4±11.4岁，男性占67.2%，16例发生了与多非利特相关的TdP（发生率0.79%）。值得注意的是，81%（13/16）的TdP病例发生在偏离FDA/制造商算法方案的患者中。同时使用活性静脉利尿剂治疗、地高辛和延长QT间期的药物是可识别的危险因素。此外，女性发生TdP的发生率（1.5%）高于男性（0.44%）{比值比[OR]3.46；P = 0.017}。
与开始使用多非利特相关的TdP总体发生率较低（0.79%）。择期住院期间遵守方案似乎非常安全。不需要同时使用静脉利尿剂、地高辛或延长QT间期药物的患者发生TdP的风险较低。
