What is the treatment for pulmonary hypertension?

Treatment of Pulmonary Hypertension

The treatment of pulmonary hypertension requires a complex strategy that includes initial evaluation of severity, appropriate drug therapy based on risk stratification, and ongoing assessment of response to treatment, with referral to specialized centers strongly recommended due to the complexity of management. 1

Classification and Initial Approach

Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure ≥25 mmHg with a pulmonary capillary wedge pressure ≤15 mmHg measured by cardiac catheterization 1. Treatment varies based on the specific classification:

• PH is categorized into 5 groups, with pulmonary arterial hypertension (PAH) being Group 1 2
• Initial evaluation should include systematic assessment using WHO functional class (FC), exercise capacity, echocardiographic parameters, laboratory values, and hemodynamic variables 1
• Risk stratification into low, intermediate, or high-risk categories based on expected 1-year mortality is essential for treatment decisions 1

General Measures and Supportive Therapy

Before specific PAH medications, several supportive measures are recommended:

• Patients should avoid pregnancy due to high mortality risk 1
• Immunization against influenza and pneumococcal infection is recommended 1
• Psychosocial support should be provided to all patients 1
• Supervised exercise training should be considered for physically deconditioned patients already on medical therapy 1
• Oxygen therapy should be considered for patients in WHO-FC III and IV with arterial blood O₂ pressure consistently <8 kPa (60 mmHg) 1
• Diuretics are indicated for patients with signs of right heart failure and fluid retention 1
• Oral anticoagulation may be considered in some PAH patients, though evidence is not conclusive 1

Specific Medical Therapy for PAH (Group 1)

Treatment strategy depends on risk stratification and vasoreactivity testing:

For Vasoreactive Patients:

• High-dose calcium channel blockers (CCBs) are recommended for patients who demonstrate acute vasoreactivity on testing 1

For Non-vasoreactive Patients:

Based on risk assessment:

Low or Intermediate Risk:

• Initial approved monotherapy or combination therapy is recommended 1
• Drugs targeting different pathways include:
  • Endothelin receptor antagonists (e.g., bosentan)
  • Phosphodiesterase type-5 inhibitors (e.g., sildenafil)
  • Soluble guanylate cyclase stimulators
  • Prostacyclin analogues and prostacyclin receptor agonists 1
• Sildenafil is FDA-approved for PAH to improve exercise capacity 3
• Epoprostenol (IV) is indicated for PAH to improve exercise capacity, particularly in patients with WHO FC III-IV symptoms 4

High Risk:

• Initial combination therapy including IV prostacyclin analogues should be considered 1
• Epoprostenol IV is particularly important for severe cases 4

Sequential Combination Therapy:

• If response to initial therapy is inadequate, sequential combination therapy should be implemented 1
• The goal is to achieve low-risk status, typically associated with WHO-FC II, good exercise capacity, and good right ventricular function 1

Treatment for Other PH Groups

• For PH due to left heart disease (Group 2) or lung diseases (Group 3): Treat the underlying condition; PAH-specific therapies are not recommended 1
• For chronic thromboembolic PH (CTEPH, Group 4):
  • Surgical pulmonary endarterectomy is recommended for operable patients 1
  • For inoperable CTEPH, balloon pulmonary angioplasty and/or targeted medical therapy should be considered 1
  • Assessment of operability should be made by a multidisciplinary team 1

Advanced Therapies

For patients with inadequate response to medical therapy:

• Lung transplantation should be considered for patients with advanced disease on maximal medical therapy 5, 6
• Extracorporeal membrane oxygenation (ECMO) may be used as a bridge to transplantation in severe cases 1

Follow-up and Treatment Goals

• Regular follow-up assessments every 3-6 months are recommended for stable patients 1
• Treatment goals include achieving WHO-FC II status, 6-minute walk distance >440m, good quality of life, and good right ventricular function 1
• Treatment should be escalated if low-risk status is not achieved during follow-up 5

Common Pitfalls and Caveats

• Avoid excessive fluid administration in patients with right ventricular failure as it may worsen cardiac function 7
• Vasopressors and inotropes, rather than fluid boluses, are often required in shock 7
• Intubation should be avoided if possible as it may worsen right heart function 7
• Abrupt discontinuation of PAH-specific therapies can lead to rapid clinical deterioration 7
• Recognize that treatment goals may not be achievable in patients with advanced disease, severe comorbidities, or elderly patients 1