Clinical efficacy of dofetilide for the treatment of atrial tachyarrhythmias in adults with congenital heart disease

Congenit Heart Dis. 2014 May-Jun;9(3):221-7. doi: 10.1111/chd.12129. Epub 2013 Aug 15.

Abstract

Background: Atrial tachyarrhythmias (AT) including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia represent a clinical challenge in the adult with congenital heart disease (CHD). Dofetilide (D) is a rapidly activating delayed rectifier potassium channel (IKr) blocker effective in pharmacological conversion and maintenance of normal sinus rhythm in patients with AF and AFL. There is limited knowledge regarding the role of D in adults with CHD.

Methods: Safety and efficacy of D was evaluated in a consecutive group of thirteen adult patients (age 40 ± 11; six women) with CHD and refractory AT.

Results: Ten patients had persistent (four AFL, one AF, and five atrial tachycardia) and three paroxysmal (one AF and two atrial tachycardia) AT. All patients were symptomatic during tachycardia, 12 patients had previously failed 2 ± 1 antiarrhythmic drugs. Mean systemic ventricular ejection fraction was 55 ± 9%; baseline QRS complex duration was 129 ± 45 ms (>120 ms in six patients). Patients were followed on D for 33 ± 39 months (median 16). Among 10 patients with persistent AT, seven patients (70%) pharmacologically converted to sinus rhythm on D and three patients (30%) required direct current cardioversion. Two patients (15.4%) experienced complete arrhythmia suppression, and seven (53.8%) experienced significant clinical improvement with sporadic recurrences; average time to recurrence was 5.5 ± 3.5 months. One patient developed torsade de pointes during loading, and the drug was discontinued. D was discontinued in five (38.5%) other patients due to recurrence of AT (n = 4) and renal failure (n = 1). Corrected QT interval (QTc) increased from 452 ± 61 to 480 ± 49 ms (P = .04) and corrected JT interval (JTc) from 323 ± 39 to 341 ± 33 ms (P = .09).

Conclusions: D should be considered a pharmacologic alternative when adult patients with CHD develop AT. D does not depress conduction, sinus node, or ventricular function but needs close monitoring for potential ventricular pro-arrhythmia.

Keywords: Atrial Tachyarrhythmias; Congenital Heart Disease; Dofetilide.

MeSH terms

  • Adult
  • Age Factors
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / physiopathology
  • Atrial Flutter / diagnosis
  • Atrial Flutter / drug therapy*
  • Atrial Flutter / etiology
  • Atrial Flutter / physiopathology
  • Female
  • Heart Defects, Congenital / complications*
  • Heart Defects, Congenital / diagnosis
  • Humans
  • Male
  • Middle Aged
  • Phenethylamines / adverse effects
  • Phenethylamines / therapeutic use*
  • Potassium Channel Blockers / adverse effects
  • Potassium Channel Blockers / therapeutic use*
  • Recurrence
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Tachycardia, Supraventricular / diagnosis
  • Tachycardia, Supraventricular / drug therapy*
  • Tachycardia, Supraventricular / etiology
  • Tachycardia, Supraventricular / physiopathology
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Arrhythmia Agents
  • Phenethylamines
  • Potassium Channel Blockers
  • Sulfonamides
  • dofetilide