Why is digoxin (digitalis glycoside) dangerous in patients with pre-excitation (Wolff-Parkinson-White syndrome) who have atrial tachyarrhythmias?

Why Digoxin is Dangerous in Pre-excitation with Atrial Tachyarrhythmias

Digoxin is contraindicated in patients with pre-excitation (Wolff-Parkinson-White syndrome) who develop atrial tachyarrhythmias because it shortens the refractory period of the accessory pathway, enabling dangerously rapid ventricular rates that can degenerate into ventricular fibrillation and sudden cardiac death. 1, 2

Primary Mechanism of Harm

Digoxin directly shortens the refractory period of the accessory pathway, which is the fundamental reason for its danger in this population 1, 3. This pharmacologic effect creates a lethal scenario when atrial fibrillation develops:

• The shortened refractory period allows more rapid antegrade conduction through the accessory pathway, bypassing the protective filtering function of the AV node 1, 2
• This can result in extremely rapid ventricular rates (often >200 bpm) that may trigger ventricular fibrillation 1, 2
• The FDA drug label explicitly warns that "after intravenous digoxin therapy, some patients with paroxysmal atrial fibrillation or flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, leading to a very rapid ventricular response or ventricular fibrillation" 2

Critical Clinical Scenario

Even patients who have never had documented atrial fibrillation remain at risk because orthodromic AVRT can spontaneously degenerate into atrial fibrillation during an episode 1, 3. This creates a dangerous situation:

• If a patient with pre-excitation on digoxin develops atrial fibrillation during what started as orthodromic AVRT, the risk of ventricular fibrillation increases dramatically 1, 3
• The ACC/AHA/HRS guidelines explicitly state that "even if AF has never been documented, AVRT may degenerate into AF. Thus, oral digoxin should not be used to treat patients with a manifest accessory pathway" 1

Guideline Recommendations

The 2015 ACC/AHA/HRS guidelines provide a Class III: Harm recommendation (meaning potentially harmful) against using digoxin in patients with pre-excited atrial fibrillation 1:

• Intravenous digoxin, oral digoxin, and other AV nodal blocking agents (IV amiodarone, beta blockers, diltiazem, verapamil) are all contraindicated in pre-excited AF 1
• These medications "may enhance conduction over the accessory pathway, increase the ventricular rate, and increase the risk of provoking a life-threatening ventricular arrhythmia" 1
• The 2014 AHA/ACC/HRS AF guidelines similarly state that "administration of intravenous amiodarone, adenosine, digoxin (oral or intravenous), or nondihydropyridine calcium channel antagonists in patients with Wolff-Parkinson-White syndrome who have pre-excited AF is potentially harmful because these drugs accelerate the ventricular rate" 1

Exception: Concealed Accessory Pathways

Digoxin may be reasonable only in patients WITHOUT pre-excitation on their resting ECG (concealed accessory pathways) who have orthodromic AVRT 1:

• In concealed pathways, there is no antegrade conduction through the accessory pathway, so the risk of rapid pre-excited ventricular rates during atrial fibrillation is eliminated 1
• However, even in this scenario, digoxin has low efficacy and should be reserved for patients who are not candidates for catheter ablation and have failed other therapies 1

Appropriate Management Alternatives

For acute management of pre-excited AF in hemodynamically stable patients, use IV procainamide or ibutilide (Class I recommendation) 1:

• These agents slow conduction over the accessory pathway and may terminate the arrhythmia 1
• Synchronized cardioversion is indicated for hemodynamically unstable patients 1

For long-term management, catheter ablation of the accessory pathway is the recommended first-line therapy (Class I recommendation) with success rates of 93-95% 1, 3:

• This definitively eliminates the risk of life-threatening arrhythmias 1
• For patients who decline or are not candidates for ablation, oral flecainide or propafenone may be used in the absence of structural heart disease 3

Key Clinical Pitfall

Never assume a patient is safe from atrial fibrillation simply because they have only experienced orthodromic AVRT in the past 1, 3. The potential for rhythm degeneration means that any patient with visible pre-excitation on ECG (manifest accessory pathway) should never receive digoxin, regardless of their arrhythmia history 1, 3, 4.