Abstract Body (Do not enter title and authors here): Background: Atrial fibrillation is the most prevalent cardiac arrhythmia, presenting symptomatic patients with a range of challenges, including diminished quality of life, heightened risk of thromboembolism, and worsening of heart failure symptoms. Dofetilide, a class 3 antiarrhythmic agent, is a proven and safe rhythm control medication employed to sustain sinus rhythm in atrial fibrillation patients. Despite its efficacy, the initial risk of QT prolongation leading to torsade de pointes (TdP) necessitates a standard protocol mandating hospitalization for three days for initiation.
Objectives: To assess safety of dofetilide when adhering to drug initiation protocol and identify traits for susceptibility to TdP in elective dofetilide admissions.
Methods: 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 meticulous 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 thorough evaluation to identify potential risk factors.
Results: Among the 2036 patients identified, mean age 66.4±11.4 years, and 67.2% male, 16 patients experienced dofetilide-related TdP, representing an 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. Females exhibited a higher incidence of TdP (1.5%) than males (0.44%) {odd ratio [OR] 3.46; P = 0.017}. Female gender emerged as a non-modifiable risk factor for dofetilide induced torsade de pointes.
Conclusion: Our study show that overall incidence of TdP related to dofetilide initiation was low (0.79%). Dofetilide initiation appears to be safe in elective hospital admissions when drug protocol is strictly followed, and concurrent use of intravenous diuretics, digoxin, or QT-prolonging drugs is avoided. Emergence of new technologies such as remote cardiac monitoring, telemedicine, “Hospital-at-home” concept make it feasible to consider out-patient initiation of dofetilide.Consideration for revision of dofetilide protocol by drug manufacturer/Food and Drug Administration is warranted to accommodate gender disparity.