What medications are appropriate to treat WHO group 2 pulmonary hypertension?

Treatment of WHO Group 2 Pulmonary Hypertension

For patients with WHO group 2 pulmonary hypertension (PH due to left heart disease), specific pulmonary arterial hypertension (PAH) medications are not recommended as they may be harmful and should be avoided. 1, 2

Understanding WHO Group 2 PH

WHO Group 2 PH is defined by:

• Mean pulmonary arterial pressure (mPAP) > 20 mmHg
• Pulmonary artery wedge pressure (PAWP) > 15 mmHg
• Underlying left heart disease as the primary cause

This category can be further classified as:

• Isolated post-capillary PH (IpcPH): PVR < 2 Wood Units
• Combined post-capillary and pre-capillary PH (CpcPH): PVR ≥ 2 Wood Units

Appropriate Treatment Approach

Primary Treatment Strategy

• Optimize treatment of the underlying left heart disease - this is the cornerstone of management
• Focus on treating:
  • Left ventricular systolic dysfunction
  • Left ventricular diastolic dysfunction
  • Valvular heart disease
  • Congenital/acquired left heart inflow/outflow tract obstructions

Specific Recommendations

1. Avoid PAH-specific medications:

   • Endothelin receptor antagonists (ERAs) like bosentan, ambrisentan, macitentan
   • Prostacyclin analogs
   • Soluble guanylate cyclase stimulators

2. PDE-5 inhibitors (sildenafil, tadalafil):

   • No general recommendation can be made for their use in WHO Group 2 PH 2
   • Some studies show reduced odds of improvement in WHO functional class with PDE-5 inhibitors in PH-LHD 3
   • May provide small benefits in 6-minute walk distance but evidence is inconsistent 3

3. Right heart catheterization:

   • Recommended when considering organ transplantation 1
   • May be considered to assist in differential diagnosis and support treatment decisions 1

Important Clinical Considerations

• WHO Group 2 PH is the most common form of pulmonary hypertension in western countries 4, 5
• Mortality is high in Group 2 PH, with 1-year and 5-year mortality rates of approximately 36.4% and 62.4%, respectively 5
• Distinguishing Group 2 PH from Group 1 PAH is critical as treatment approaches differ completely 4

Common Pitfalls to Avoid

1. Misdiagnosis: Carefully differentiate between Group 1 PAH and Group 2 PH, especially in patients with heart failure with preserved ejection fraction (HFpEF)

2. Inappropriate medication use: Despite increasing prescription of PAH-specific therapies in patients with Group 2 PH, this practice is not supported by evidence and may be harmful 5

3. Vasoreactivity testing: This is not recommended in PH groups 2,3,4, and 5 1

4. Overlooking left heart disease: When PAWP measurement is unreliable, left heart catheterization should be considered to measure left ventricular end-diastolic pressure (LVEDP) 1

By focusing treatment on the underlying left heart disease and avoiding PAH-specific medications that may be harmful, outcomes for patients with WHO Group 2 PH can be optimized.