Treatment of Severe Pulmonary Hypertension
For severe (high-risk) pulmonary arterial hypertension, initiate intravenous epoprostenol immediately, as it is the only therapy proven to improve survival in this population. 1
Initial Diagnostic Confirmation and Risk Assessment
Before initiating any PAH-specific therapy, right heart catheterization must be performed to confirm the diagnosis and establish hemodynamic classification 2, 3. This is non-negotiable, as treatment decisions depend entirely on accurate hemodynamic assessment.
Risk stratification is critical and should incorporate multiple parameters 2:
- WHO functional class (target: I-II)
- 6-minute walk distance (target: >440 meters)
- BNP/NT-proBNP levels (target: BNP <50 ng/L or NT-proBNP <300 ng/L)
- Right atrial pressure and cardiac index from catheterization
- Echocardiographic findings (TAPSE >20mm, no pericardial effusion)
Treatment Algorithm Based on Severity
High-Risk (Severe) PAH
Intravenous prostacyclin analogues, specifically epoprostenol, are mandatory 1. This is the only therapy with proven survival benefit in severe PAH and should be initiated at 2 ng/kg/min via continuous central venous infusion, with dose escalation in 2 ng/kg/min increments every 15 minutes until dose-limiting effects occur 4.
Critical warning: Never abruptly discontinue or reduce epoprostenol dosing, as this can lead to rapid clinical deterioration and death 4. Patients require continuous infusion via central venous catheter using an ambulatory pump 4.
Low or Intermediate-Risk PAH
Initial oral combination therapy is recommended over monotherapy 2, 1. This typically involves:
- Endothelin receptor antagonist PLUS phosphodiesterase-5 inhibitor 3
- Sequential combination therapy should be added if inadequate response occurs 2
Vasoreactive PAH (Small Subset)
Vasoreactivity testing during right heart catheterization is essential for patients with idiopathic, heritable, or drug-induced PAH 2, 5. A positive response (≥10 mmHg fall in mean PAP to ≤40 mmHg with stable/increased cardiac output) identifies candidates for high-dose calcium channel blockers (nifedipine or diltiazem) 5.
Essential Supportive Care for Severe PH
Regardless of specific PAH therapy, all patients with severe PH require:
Diuretics for volume management: Furosemide with careful monitoring of electrolytes and renal function for right ventricular failure and fluid retention 1, 3
Oxygen supplementation: Continuous oxygen when saturation falls below 90% or PaO2 <60 mmHg 3
Pregnancy avoidance: Absolute contraindication due to 30-50% mortality risk 2, 1
Monitoring and Treatment Escalation
Regular follow-up assessments every 3-6 months are mandatory in stable patients 2, 5. The treatment goal is achieving and maintaining low-risk status across all parameters 3, 5.
If inadequate response to initial therapy occurs, sequential combination therapy targeting multiple pathways is required 2, 1. For patients failing maximal medical therapy, early referral for lung transplantation evaluation is essential 1, 3.
Critical Pitfalls to Avoid
Do not use PAH-approved therapies in patients with pulmonary hypertension due to left heart disease or lung diseases 2. These medications may worsen outcomes in these populations 6.
All severe PAH patients must be managed at specialized pulmonary hypertension centers with multidisciplinary teams including cardiology, pulmonology, nursing specialists, and appropriate on-call expertise 2, 1. Early consultation and transfer to tertiary centers with invasive monitoring capabilities is advised for severe cases 7.
For chronic thromboembolic pulmonary hypertension (CTEPH), the treatment paradigm differs entirely: surgical pulmonary endarterectomy in deep hypothermia circulatory arrest is the treatment of choice, with decisions made by multidisciplinary expert teams 2, 1. Riociguat is reserved for inoperable CTEPH or persistent/recurrent PH after surgery 1.