Deshmukh Amrish, Yokokawa Miki, McBride Daniel, Simpson Jamie, Chou Andrew, Ghannam Michael, Liang Jackson J, Saeed Mohammed, Cunnane Ryan, Ghanbari Hamid, Latchamsetty Rakesh, Crawford Thomas, Jongnarangsin Krit, Pelosi Frank, Chugh Aman, Morady Fred, Bogun Frank, Oral Hakan
Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, Michigan, USA.
Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan, USA.
J Cardiovasc Electrophysiol. 2024 Dec;35(12):2363-2371. doi: 10.1111/jce.16452. Epub 2024 Oct 3.
Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it has been used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardias (VTs).
The purpose of this study was to determine the efficacy and safety of dofetilide for ventricular arrythmias (VAs).
In this retrospective cohort study, 81 patients (59 men; age = 60 ± 14 years; LVEF = 0.34 ± 0.16) were admitted for dofetilide initiation to treat PVCs (29), VTs (42) or both (10). A ≥ 80% decrease in PVC burden was defined as a satisfactory response. An ICD was present in 72 patients (89%). Another antiarrhythmic was previously used in 50 patients (62%). Prior catheter ablation had been performed in 33 patients (41%).
During intitiation, dofetilide was discontinued in 12 patients (15%) due to QT prolongation (8) and inefficacy to suppress VAs (4). Among the 32 patients with PVCs who successfully started dofetilide, the mean PVC burden decreased from 20 ± 10% to 8 ± 8% at a median follow-up of 2.6 months (p < .001). PVC burden was reduced by ≥80% in only 11/32 patients (34%). During 7 ± 1 years of follow-up, 41/69 patients (59%) continued to have VAs and received appropriate ICD therapies for monomorphic VTs (35) and polymorphic VT/VF (6) at a median of 8.0 (IQR 2.6-33.2) months. Dofetilide had to be discontinued in 50/69 patients (72%) due to inefficacy or intolerance. The composite outcome of VT/VF recurrence, heart transplantation, or death occurred in 6/12 patients (50%) without dofetilide and 49/69 patients (71%) with dofetilide. The event free survival was similar between patients treated with and without dofetilide (log-rank p = .55).
Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress the occurrence of VTs in a majority of patients.
多非利特是一种III类抗心律失常药物，已被批准用于治疗心房颤动和心房扑动。鉴于其他III类药物的疗效，它已被用于非标签治疗室性早搏（PVC）和室性心动过速（VT）。
本研究的目的是确定多非利特治疗室性心律失常（VA）的疗效和安全性。
在这项回顾性队列研究中，81例患者（59例男性；年龄=60±14岁；左心室射血分数[LVEF]=0.34±0.16）因开始使用多非利特治疗PVC（29例）、VT（42例）或两者（10例）而入院。PVC负荷降低≥80%被定义为满意反应。72例患者（89%）植入了植入式心律转复除颤器（ICD）。50例患者（62%）曾使用过另一种抗心律失常药物。33例患者（41%）曾接受过导管消融术。
在起始治疗期间，12例患者（15%）因QT间期延长（8例）和抑制VA无效（4例）而停用多非利特。在成功开始使用多非利特的32例PVC患者中，中位随访2.6个月时，平均PVC负荷从20±10%降至8±8%（p<0.001）。仅11/32例患者（34%）的PVC负荷降低≥80%。在7±1年的随访期间，69例患者中有41例（59%）继续有VA，并在中位时间8.0（四分位间距2.6-33.2）个月时接受了针对单形性VT（35例）和多形性VT/室颤（VF）（6例）的适当ICD治疗。由于无效或不耐受，69例患者中有50例（72%）不得不停用多非利特。在未使用多非利特的12例患者中有6例（50%）以及使用多非利特的69例患者中有49例（71%）发生了VT/VF复发、心脏移植或死亡的复合结局。使用和未使用多非利特的患者无事件生存率相似（对数秩检验p=0.55）。
多非利特治疗可使PVC减少，但仅有少数患者出现具有临床意义的抑制。大多数患者中，多非利特未能抑制VT的发生。
