Naksuk Niyada, Sugrue Alan M, Padmanabhan Deepak, Kella Danesh, DeSimone Christopher V, Kapa Suraj, Asirvatham Samuel J, Lee Hon-Chi, Ackerman Michael J, Noseworthy Peter A
Department of Cardiovascular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
Division of Cardiology, Department of Internal Medicine, University of Illinois at Chicago, Chicago, IL, USA.
J Interv Card Electrophysiol. 2019 Mar;54(2):189-196. doi: 10.1007/s10840-018-0476-2. Epub 2018 Oct 23.
There is a significant variation in the clinical approach of initiation and dose adjustment of dofetilide in atrial fibrillation (AF). Excessive QT prolongation could predispose patients to torsades de pointes (TdP), which can be fatal.
We performed a retrospective case-control study at Mayo Clinic Rochester (January 1, 2003 to December 31, 2016). "TdP risk" cases were defined as patients on dofetilide therapy for AF with subsequent TdP or excessive QTc prolongation requiring dose reduction or discontinuation (N = 31). A control group was matched 1:1 with cases by age, gender, year of admission, and dofetilide dose (N = 31).
Using multivariate regression analysis, independent predictors of TdP risk included baseline QTc exceeding recommendations (adjusted odd ratio [AOR] 4.57; P = 0.023); underlying AF with rapid ventricular rate (AOR 16.95; P = 0.004); and diuretic therapy for acute heart failure (AOR 8.42; P = 0.007). Poor inter-observer agreement was identified among QT interval measurement in patients with AF and rapid ventricular rate compared to those in rate controlled AF or sinus rhythm. TdP risk cases receiving diuretics for acute heart failure had a significant decline in creatinine clearance than controls, although serum electrolytes and replacement did not differ among the two groups.
Excessive QTc prolongation and AF with rapid ventricular rate at time of dofetilide initiation (likely due to difficulty in measuring QT intervals), and diuretic therapy for acute heart failure were independent factors for dofetilide-related TdP risk. Based on these data, possible preventive strategies could be adapted for safety protocols among hospitalized patients.
在心房颤动（AF）患者中，决奈达隆起始治疗及剂量调整的临床方法存在显著差异。QT间期过度延长会使患者易发生尖端扭转型室性心动过速（TdP），这可能是致命的。
我们在梅奥诊所罗切斯特院区进行了一项回顾性病例对照研究（2003年1月1日至2016年12月31日）。“TdP风险”病例定义为接受决奈达隆治疗AF后发生TdP或QTc过度延长需减量或停药的患者（N = 31）。对照组按年龄、性别、入院年份和决奈达隆剂量与病例1:1匹配（N = 31）。
使用多因素回归分析，TdP风险的独立预测因素包括基线QTc超过推荐值（校正比值比[AOR] 4.57；P = 0.023）；伴有快速心室率的基础AF（AOR 16.95；P = 0.004）；以及用于急性心力衰竭的利尿剂治疗（AOR 8.42；P = 0.007）。与心率控制的AF或窦性心律患者相比，伴有快速心室率的AF患者QT间期测量的观察者间一致性较差。接受急性心力衰竭利尿剂治疗的TdP风险病例肌酐清除率较对照组显著下降，尽管两组血清电解质及补充情况无差异。
决奈达隆起始治疗时QTc过度延长和伴有快速心室率的AF（可能由于QT间期测量困难），以及用于急性心力衰竭的利尿剂治疗是与决奈达隆相关的TdP风险的独立因素。基于这些数据，可针对住院患者的安全方案采用可能的预防策略。
