Idiopathic/heritable pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (IPAH) and heritable pulmonary arterial hypertension (HPAH) are rare, progressive conditions characterized by abnormally elevated blood pressure in the pulmonary arteries — the blood vessels that carry blood from the heart to the lungs. In IPAH, no identifiable cause is found, while HPAH is associated with genetic mutations, most commonly in the BMPR2 (bone morphogenetic protein receptor type 2) gene. These conditions were formerly known as primary pulmonary hypertension (PPH). The elevated pulmonary arterial pressure results from narrowing, stiffening, and remodeling of the small pulmonary arteries, which forces the right side of the heart to work progressively harder to pump blood through the lungs. Key symptoms include progressive shortness of breath (dyspnea), especially during physical activity, fatigue, chest pain, dizziness, fainting episodes (syncope), and swelling of the ankles and legs (peripheral edema). As the disease advances, the right ventricle of the heart becomes enlarged and weakened, eventually leading to right heart failure if untreated. Patients may also experience palpitations and cyanosis (bluish discoloration of the skin due to low oxygen levels). While there is no cure, significant advances in treatment have improved survival and quality of life. Current therapies target three major molecular pathways: the endothelin pathway (endothelin receptor antagonists such as bosentan and ambrisentan), 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. Lung transplantation remains an option for patients with severe disease refractory to medical therapy. Genetic counseling is recommended for families with HPAH.

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

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