What is the initial treatment for pulmonary hypertension?

Initial Treatment for Pulmonary Hypertension

The initial treatment for pulmonary hypertension should include general measures, supportive therapy, and referral to expert centers, followed by specific medication therapy based on vasoreactivity testing results. 1, 2

Treatment Approach

Step 1: Initial Approach

1. General Measures:

   • Physical activity with supervised rehabilitation
   • Pregnancy avoidance (Class I recommendation)
   • Immunization against influenza and pneumococcal infection (Class I)
   • Psychosocial support (Class I)
   • Avoid excessive physical activity that leads to distressing symptoms 1

2. Supportive Therapy:

   • Oral anticoagulants
   • Diuretics for fluid overload
   • Oxygen supplementation (particularly for patients with WHO-FC III and IV with arterial blood O₂ pressure <60 mmHg)
   • Digoxin (in selected cases) 1, 2

3. Referral to Expert Centers:

   • Treatment should be managed by a multidisciplinary team at specialized centers with expertise in pulmonary hypertension
   • Centers should have essential facilities including specialized PH ward, ICU, outpatient service, and advanced diagnostic capabilities 2

4. Acute Vasoreactivity Testing:

   • Mandatory to identify patients who may respond to calcium channel blockers
   • Performed during right heart catheterization 2

Step 2: Specific Medication Therapy

For Vasoreactive Patients:

• High-dose calcium channel blockers (only for patients who demonstrate positive acute vasoreactivity testing)
• The American College of Cardiology warns against using calcium channel blockers in non-responders due to potential severe hemodynamic compromise and death 2

For Non-Vasoreactive Patients: Based on risk stratification (low, intermediate, or high risk):

1. First-line options:

   • Phosphodiesterase type-5 inhibitors (e.g., sildenafil 20mg three times daily)
   • Endothelin receptor antagonists (e.g., bosentan, ambrisentan, macitentan)
   • Soluble guanylate cyclase stimulators (e.g., riociguat) 2

2. For more severe cases:

   • Prostacyclin analogs:
     • Epoprostenol (IV) - initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes until dose-limiting effects or tolerance is established 3
     • Treprostinil (available in intravenous, subcutaneous, and inhaled forms) 2

Risk Stratification to Guide Therapy

Treatment decisions should be guided by risk assessment using multiple parameters:

Parameter	Low Risk	Intermediate Risk	High Risk
Clinical signs of RV failure	Absent	Absent	Present
WHO functional class	I-II	III	IV
6MWD	>440m	165-440m	<165m
BNP	<50 ng/L	50-300 ng/L	>300 ng/L
NT-proBNP	<300 ng/L	300-1400 ng/L	>1400 ng/L

Monitoring and Follow-up

• Regular follow-up every 3-6 months for stable patients
• Assessment should include clinical evaluation, exercise capacity testing, biomarkers, and echocardiography
• Treatment goals: WHO FC I-II status, 6MWD >440m, normal/near-normal RV function, and low BNP/NT-proBNP levels 2

Important Considerations and Pitfalls

• Avoid abrupt withdrawal of pulmonary hypertension medications as this can lead to clinical deterioration and death
• Avoid nonselective vasodilators including nitrates in patients with pulmonary hypertension due to potential severe systemic hypotension and worsening of right ventricular failure
• Avoid serotonergic drugs with 5-HT2B receptor activity and tyrosine kinase inhibitors (e.g., dasatinib) as they may cause or worsen pulmonary arterial hypertension
• Monitor liver function monthly in patients on bosentan due to 3-5% risk of liver function abnormalities
• Prefer inotropes over fluid boluses in cases of right ventricular failure, as fluid boluses may worsen the condition 2

Advanced Therapies for Refractory Cases

• Combination therapy with multiple pulmonary hypertension-specific medications
• Lung transplantation for patients with inadequate response to maximum medical therapy
• Atrial septostomy as a palliative procedure or bridge to transplantation in patients with refractory right heart failure
• Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH) 2