Risk Factors Associated with Unsuccessful Dofetilide Initiation Due to Excessive QT Interval Prolongation: A Retrospective Study

Dofetilide is a class III anti-arrhythmic medication approved for patients with atrial fibrillation to maintain sinus rhythm. Excessive QTc interval prolongation, a potential side effect of dofetilide, increases the risk of torsades de pointes. This risk is mitigated by closely monitoring the QTc interval during an inpatient initiation protocol for the first five doses. Prior studies have demonstrated that dofetilide can be safely used in patients with heart failure after completing the initiation protocol. However, no studies have investigated risk factors associated with dofetilide-induced excessive QTc interval prolongation, resulting in discontinuation of the medicine. This single-center retrospective cohort study analyzed the association between dofetilide-associated excessive QTc prolongation during medication initiation and pertinent medical comorbidities as well as various echocardiographic values of interest. Risk factors found to be significantly associated with excessive QTc prolongation during dofetilide initiation included a clinical history of heart failure, reduced left ventricular ejection fraction, increased left ventricular end-diastolic diameter, increased left atrial diameter, and reduced right ventricular systolic function. Although some studies have demonstrated the safety of dofetilide use in patients with heart failure, our findings suggest that these patients are less likely to tolerate initiation of the medication due to excessive QTc prolongation.