Epidemiology

Etiology

Pulmonary arterial hypertension (Group 1 PH)

• Idiopathic
• Hereditary (e.g., BMPR2 loss-of-function mutation)
  • Encodes a set of inhibitors of vascular smooth muscle cell proliferation
  • Associated with a poor prognosis
• Drug-induced
  • Methamphetamine (and possibly amphetamines and cocaine)
• Associated conditions
  • Connective tissue diseases, e.g., systemic sclerosis
  • Portopulmonary hypertension
  • Congenital heart disease (e.g., left-to-right shunt, Eisenmenger syndrome)
  • HIV infection
  • Schistosomiasis

Pathophysiology

Clinical features

Diagnostics

• Thickening of the right ventricular free wall
  • Normal heart

Treatment

Group 1 PH: PAH

• Calcium channel blockers: First-line pulmonary vasodilator therapy for patients with PAH and positive vasoreactivity testing
• Other pulmonary vasodilator therapies: typically second-line agents, the choice of which depends on symptom severity
  • Endothelin receptor antagonists (e.g., bosentan, macitentan, ambrisentan)
    • Competitively inhibit endothelin-1 receptors �?�?vasoconstriction in the pulmonary circuit
  • Phosphodiesterase-5 inhibitors (e.g., sildenafil)
    • PDE5 inhibition �?�?breakdown of cGMP �?pulmonary vasodilation, penile smooth muscle relaxation, and �?blood flow
  • Prostacyclin analogs (iloprost, treprostinil) OR Synthetic prostacyclin (epoprostenol)
    • Prostacyclin (PGI2) acts as a direct vasodilator (systemic and pulmonary) and inhibits platelet aggregation via prostacyclin receptors.
    • Receptor binding of prostacyclins or prostacyclin analogs �?�?intracellular cAMP �?inhibition of myosin light chain kinase �?vascular smooth muscle relaxation