Pathophysiology

Increased pressure in pulmonary circuit → ↑ right ventricular afterload → dilatation and/or hypertrophy of the right heart → right heart failure and arrhythmias → death

• Increased pulmonary vascular resistance

  • Occlusive vasculopathy (e.g., idiopathic pulmonary arterial hypertension, connective tissue diseases)

  • Hypoxic pulmonary vasoconstriction: chronic hypoxic pulmonary vasoconstriction → airway smooth muscle hypertrophy (medial hypertrophy) and pulmonary vascular bed destruction → ↑ pulmonary vascular resistance (e.g., COPD, obstructive sleep apnea)

  • Increased pulmonary vessel pressure → right heart hypertrophy → right heart failure (cor pulmonale) and arrhythmias → death

  • Inflammation (e.g., COPD) → ↑ inflammatory cell infiltration of intima → thickened endothelial wall → intimal fibrosis

  • PAH associated with endothelial dysfunction: ↑ endothelin and ↓ vasodilators (e.g., NO, prostacyclins) → vasoconstriction → arteriosclerosis, plexiform lesions [13]

• Increased pulmonary venous pressure: volume or pressure overload from left-sided heart disease (e.g. mitral valve regurgitation)

• Increased pulmonary blood flow

  • Left-to-right shunt (e.g., ASD, VSD, PDA)

  • Portopulmonary hypertension

  • Sickle cell anemia: Individuals with SCD have an anemia-induced increase in cardiac output.