Idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (IPAH), formerly known as primary pulmonary hypertension (PPH), is a rare and serious condition characterized by abnormally elevated blood pressure in the pulmonary arteries — the blood vessels that carry blood from the heart to the lungs. In IPAH, the small pulmonary arteries become narrowed, thickened, and stiffened due to vascular remodeling, including smooth muscle cell proliferation, endothelial dysfunction, and in situ thrombosis. This increased resistance forces the right ventricle of the heart to work progressively harder to pump blood through the lungs, eventually leading to right heart failure if untreated. The term 'idiopathic' indicates that no identifiable underlying cause or known genetic mutation has been found, distinguishing it from heritable pulmonary arterial hypertension (HPAH) and other forms of PAH associated with connective tissue diseases, congenital heart defects, or drug exposure. Key symptoms include progressive exertional dyspnea (shortness of breath during physical activity), fatigue, chest pain, dizziness, syncope (fainting), and peripheral edema (swelling of the ankles and legs). As the disease advances, patients may experience worsening exercise intolerance and signs of right heart failure, including abdominal distension from ascites and hepatomegaly. The condition predominantly affects the cardiovascular and pulmonary systems. The treatment landscape for IPAH has expanded significantly over the past two decades. Current therapies target three major pathways involved in pulmonary vascular disease: the endothelin pathway (endothelin receptor antagonists such as bosentan, ambrisentan, and macitentan), the nitric oxide pathway (phosphodiesterase-5 inhibitors such as sildenafil and tadalafil, and soluble guanylate cyclase stimulators such as riociguat), and the prostacyclin pathway (prostacyclin analogues such as epoprostenol, treprostinil, and iloprost, and the prostacyclin receptor agonist selexipag). Combination therapy using drugs from multiple pathways is now standard of care. Calcium channel blockers may be effective in a small subset of patients who demonstrate acute vasoreactivity. For patients with refractory disease, lung transplantation or combined heart-lung transplantation remains an option. Despite these advances, IPAH remains a progressive disease with no cure, and early diagnosis and treatment are critical for improving outcomes and quality of life.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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