Pulmonary Arterial Hypertension

Definition

Pulmonary Arterial Hypertension (PAH) is a progressive disorder characterized by elevated pulmonary arterial pressure and vascular resistance, leading to right ventricular failure if untreated. It is defined as mean pulmonary arterial pressure ≥20 mmHg at rest, with pulmonary vascular resistance ≥3 Wood units and pulmonary capillary wedge pressure ≤15 mmHg.

Epidemiology

• Rare disease with prevalence of 15–50 cases per million adults
• More common in women than men (female-to-male ratio ~4:1)
• Can occur at any age, but most commonly diagnosed in adults 30–60 years
• Idiopathic PAH accounts for a significant proportion of cases
• Associated with connective tissue diseases, congenital heart disease, portal hypertension, and HIV

Etiology

• Idiopathic (most common)
• Heritable (mutations in BMPR2, ALK1, or other genes)
• Associated with connective tissue disease (e.g., scleroderma)
• Congenital heart disease with systemic-to-pulmonary shunts
• Drug- and toxin-induced (e.g., anorexigens, methamphetamines)
• HIV infection or portal hypertension-associated PAH

Pathophysiology

• Vasoconstriction of pulmonary arteries
• Vascular remodeling with intimal proliferation and medial hypertrophy
• Thrombosis in situ in small pulmonary arteries
• Increased pulmonary vascular resistance leading to elevated right ventricular afterload
• Right ventricular hypertrophy and eventual failure
• Reduced cardiac output and impaired oxygen delivery
• Progressive disease ultimately causes dyspnea, fatigue, and right heart failure