What is the role of digoxin in treating pulmonary hypertension (PH), particularly in patients with right ventricular dysfunction or heart failure?

Role of Digoxin in Pulmonary Hypertension with Right Ventricular Dysfunction

Digoxin should be limited to patients with pulmonary hypertension who develop atrial tachyarrhythmias requiring rate control, as there is no evidence supporting its routine use for right ventricular dysfunction in pulmonary hypertension. 1

Current Evidence and Recommendations

The European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines clearly state that digoxin has only been shown to improve cardiac output acutely in idiopathic pulmonary arterial hypertension (IPAH), while its efficacy when administered chronically remains unknown 1. The guidelines specifically mention that digoxin "may be given to slow ventricular rate in patients with PAH who develop atrial tachyarrhythmias" 1.

Similarly, the American College of Cardiology Foundation (ACCF) consensus document notes that digoxin is "sometimes used in those patients with right heart failure and a low cardiac output and in patients with atrial arrhythmias" 1.

Acute vs. Chronic Effects

• Acute effects: Research has demonstrated that intravenous digoxin administration in patients with pulmonary hypertension produces a modest increase in cardiac output and reduces circulating norepinephrine levels 2.

• Chronic effects: A recent retrospective study from 2023 found that chronic digoxin use in PAH patients was associated with:

  • Higher combined all-cause mortality or heart failure hospitalization (HR 1.82)
  • Increased all-cause mortality (HR 1.92)
  • More heart failure hospitalizations (HR 1.89)
  • Worse transplant-free survival (HR 2.00) 3

This concerning data suggests potential harm with chronic digoxin use in PAH, even after adjusting for patient characteristics and disease severity.

Clinical Application

When considering digoxin in pulmonary hypertension:

1. Primary indication: Rate control for atrial tachyarrhythmias in PAH patients 1

2. Not recommended for:

   • Routine treatment of right ventricular dysfunction in PAH
   • Primary therapy for stabilization of acute decompensation
   • Patients with significant sinus or atrioventricular block without a pacemaker 1

3. Dosing considerations (if used for arrhythmia control):

   • Initial dose: 0.125-0.25 mg daily
   • Lower doses (0.125 mg daily or every other day) for patients >70 years, with impaired renal function, or low lean body mass
   • Target serum concentration: 0.5-0.9 ng/mL 1, 4

Monitoring and Precautions

If digoxin is used for atrial arrhythmias in PAH patients:

• Monitor serum electrolytes (especially potassium) and renal function
• Watch for signs of toxicity (arrhythmias, visual disturbances, nausea)
• Use cautiously with other drugs that affect digoxin levels or depress nodal function
• Consider drug interactions with other PAH medications 1, 4

Alternative Approaches

For right ventricular dysfunction in PAH, guidelines recommend:

• Diuretics for RV failure with fluid retention (Class I recommendation) 1
• Oxygen therapy when arterial blood O₂ pressure is consistently <60 mmHg 1
• PAH-specific therapies (prostanoids, endothelin receptor antagonists, PDE-5 inhibitors)
• Consider iron supplementation if deficient 1

Conclusion

While digoxin may improve cardiac output acutely in PAH patients, recent evidence suggests potential harm with chronic use. Its role should be limited to rate control in PAH patients with atrial tachyarrhythmias, and it should not be routinely used for right ventricular dysfunction in pulmonary hypertension.