Should digoxin be avoided in all patients with pre-excitation or just those with atrial fibrillation and pre-excitation?

Digoxin Use in Patients with Pre-excitation

Digoxin should be avoided in all patients with pre-excitation (Wolff-Parkinson-White syndrome), regardless of whether they have atrial fibrillation or not, due to the risk of potentially life-threatening ventricular arrhythmias. 1

Rationale for Avoiding Digoxin in All Pre-excitation Cases

• Digoxin shortens the refractory period of the accessory pathway, which can lead to increased conduction through the pathway and potentially dangerous ventricular rates 1
• Even in patients without documented atrial fibrillation, orthodromic AVRT (atrioventricular reentrant tachycardia) can spontaneously degenerate into atrial fibrillation during an episode 1
• If atrial fibrillation develops in a patient with pre-excitation who is taking digoxin, the risk of ventricular fibrillation is significantly increased due to enhanced accessory pathway conduction 1
• The American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines explicitly state that oral digoxin is "potentially harmful for ongoing management in patients with AVRT or AF and pre-excitation on their resting ECG" 1

Mechanisms of Harm

• Digoxin increases ventricular rate by shortening the refractory period of the accessory pathway 1
• In pre-excited AF, digoxin can facilitate rapid conduction through the accessory pathway, potentially leading to ventricular fibrillation 1
• Even in patients with only orthodromic AVRT (without AF), the risk remains because:
  • AVRT can spontaneously convert to AF during an episode 1
  • The shortened refractory period of the accessory pathway from digoxin would make this conversion particularly dangerous 1

Alternative Management Options

• Catheter ablation of the accessory pathway is the recommended first-line therapy for patients with pre-excitation who have experienced arrhythmias (Class I recommendation) 1
• For acute management of pre-excited AF in hemodynamically stable patients:
  • IV procainamide or ibutilide are recommended (Class I) 1
  • These medications slow conduction over the accessory pathway and may terminate AF 1
• For ongoing management in patients who are not candidates for ablation:
  • Oral flecainide or propafenone may be used in patients without structural heart disease 1
  • Oral beta-blockers, diltiazem, or verapamil may be considered for orthodromic AVRT in patients with pre-excitation, but must be used with caution due to the risk of AF development during AVRT 1

Clinical Pitfalls to Avoid

• Never use digoxin in any patient with known pre-excitation, even if they have never had documented AF 1
• Avoid other medications that can enhance accessory pathway conduction during AF, including:
  • IV amiodarone 1
  • IV/oral beta blockers 1
  • IV/oral diltiazem and verapamil 1
• These medications may increase ventricular rate through different mechanisms than digoxin (e.g., drug-induced hypotension with increased catecholamines) but pose similar risks 1
• Remember that patients with pre-excitation may develop AF during an episode of AVRT, so the risk of rapid conduction through the accessory pathway exists even in patients who have only had AVRT 1

Evidence Quality Assessment

• The recommendation to avoid digoxin in all pre-excitation patients is based on Class III: Harm recommendation with Level of Evidence C-LD (limited data) from the ACC/AHA/HRS guidelines 1
• While large randomized controlled trials are lacking, the potential for life-threatening harm makes stronger evidence ethically challenging to obtain 1
• The physiological mechanism of harm is well-established and consistent with observed clinical outcomes 1