What is pulmonary arterial hypertension?

Pulmonary arterial hypertension (PAH) is a rare and serious condition in which the small blood vessels in the lungs become narrowed, stiffened, and damaged. The result is high blood pressure inside the lung circulation, which strains the right side of the heart. Over time, the right heart can fail under the persistent strain.

Why it is distinct. PAH is one form of pulmonary hypertension and is defined by specific changes in the pulmonary blood vessels (Group 1 in the formal classification). Pulmonary hypertension can also occur because of left heart disease, lung disease, blood clots in the lungs, or other causes, and the management is different in each case. Distinguishing PAH from the other groups is important because the modern therapy is specifically for PAH.

The biology. The narrowed pulmonary blood vessels are caused by an imbalance of signals that normally keep the vessels open and healthy. Three main pathways are involved (endothelin, nitric oxide, and prostacyclin), and a fourth (activin signalling) was identified more recently. Modern therapy targets these pathways.

The therapy approach. PAH is now treated with combination therapy from the start in most newly-diagnosed patients. Specific medications work on each of the pathways, and combining them produces better outcomes than using one alone.

Endothelin receptor antagonists relax the pulmonary blood vessels by blocking a constricting signal.

PDE5 inhibitors and a related medicine (riociguat) increase nitric oxide signalling, which also relaxes the blood vessels.

Prostacyclin pathway agents replace or mimic prostacyclin, a substance that opens blood vessels and prevents clotting. They come in oral, inhaled, sub-cutaneous, and intravenous forms.

Activin-pathway therapy (sotatercept) is the newest class and works on the underlying remodelling biology rather than just relaxing blood vessels.

What to expect. PAH is a serious condition but modern therapy has substantially improved outcomes. With appropriate combination therapy and care at a specialist PAH centre, many patients live for many years with manageable symptoms. Lung transplant remains an option for patients with end-stage disease.