Pulmonary Arterial Hypertension

Early diagnosis is challenging because symptoms are non-specific and progress gradually. Patients often present with exertional dyspnea, fatigue, chest pain, syncope, or right heart failure signs. The diagnostic process involves the followings:

Clinical Evaluation and History

Detailed medical history and physical examination help uncover risk factors, associated conditions, and disease progression.

Non-Invasive Tests

• Electrocardiogram (ECG): May reveal right ventricular hypertrophy or right axis deviation.
• Chest X-ray: Can show enlarged pulmonary arteries and right heart enlargement.
• Echocardiography: Primary screening tool to estimate pulmonary artery pressures and assess right ventricular size/function.
• Pulmonary Function Tests: Used to rule out underlying lung disease.
• Blood Tests: Evaluate for connective tissue disease, liver function, HIV, and related conditions.
• Six-Minute Walk Test (6MWT): Measures exercise capacity and functional class.

Invasive Testing

• Right Heart Catheterization: The gold standard. Confirms the diagnosis by measuring resting mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg, and elevated pulmonary vascular resistance (> 2 Wood units).
• Vasoreactivity Testing: Uses agents like inhaled nitric oxide to evaluate for acute vasoreactivity, which can guide therapy.

Differential Diagnosis

Other causes of pulmonary hypertension, such as left heart disease, lung disease, or chronic thromboembolic pulmonary hypertension (CTEPH), must be excluded.

Management includes general measures, supportive care, and pharmacological therapies aimed at improving symptoms, quality of life, and survival.

General Measures and Supportive Care

• Supervised physical activity as tolerated
• Oxygen therapy for hypoxemia
• Diuretics for fluid overload and edema
• Anticoagulation (in some patients)
• Immunizations (e.g., influenza, pneumococcus)
• Pregnancy avoidance or counseling (due to high maternal mortality risk)

Pharmacologic Therapies

PAH-specific drugs target the endothelin, nitric oxide, and prostacyclin pathways:

• Calcium Channel Blockers (CCBs): Only for patients with a positive vasoreactivity test (minority of patients), e.g., amlodipine, nifedipine.
• Endothelin Receptor Antagonists (ERAs): Bosentan, ambrisentan, macitentan.
• Phosphodiesterase-5 Inhibitors (PDE5i): Sildenafil, tadalafil.
• Soluble Guanylate Cyclase (sGC) Stimulators: Riociguat.
• Prostacyclin Analogues and Receptor Agonists: Epoprostenol, treprostinil, iloprost, selexipag.
• Combination Therapy: Using agents from different classes.
• Sotatercept: A newly approved therapy, sotatercept acts as a selective ligand trap for TGF-β superfamily members, correcting signaling imbalances involved in vascular remodeling. Clinical trials have demonstrated significant improvements in exercise capacity, pulmonary vascular resistance, and other outcomes when added to standard therapy. Sotatercept represents a major advance in disease-modifying therapy for PAH.

Advanced Therapies and Interventions

• Atrial Septostomy: Rarely used, creates a right-to-left interatrial shunt to reduce right heart pressure.
• Lung Transplantation: For advanced, treatment-refractory cases (single or double lung transplant).