Review says therapies boost PAH survival


A new review article shows positive trends in survival as scientists better understand the different types and symptoms of pulmonary arterial hypertension (PAH).

Untreated, pulmonary arterial hypertension (PAH) often leads to right heart failure and death. However, recent advances in diagnosing and treating the disease have dramatically increased patient survival rates, according to a new review article published in Journal of the American Medical Association.

In the United States, about 10.6 cases of PAH occur per 1 million adults, the authors wrote. PAH occurs when increased pulmonary vascular resistance raises pressure in the pulmonary arteries, but its symptoms are nonspecific. The authors stated that exertional dyspnea and fatigue are 2 common symptoms. Thus, they stated that patients with unexplained dyspnea should be evaluated for PAH.

One of the reasons that diagnosing PAH can be complicated is that it is one of 5 subcategories of pulmonary hypertension, defined as mean pulmonary arterial pressure greater than 20 mm Hg. L PAH is distinguished by a pulmonary artery wedge pressure of 15 mm Hg or less and a pulmonary vascular resistance of 3 Wood’s units or greater, the authors said. However, PAH itself can be divided into several subgroups based on its underlying etiology.

These subgroups include idiopathic PAH, which the authors say meets the technical definition of PAH but lacks other disease processes, such as collagen vascular disease or liver disease. About 4 in 10 patients fall into this category, although the exact rate varies between studies.

Between 6% and 10% of patients have hereditary or familial PAH, most often associated with BMPR2 embarrassed. Other patients have PAH due to drugs or toxins, including methamphetamine and dasatinib (Sprycel).

Yet another subgroup are patients whose PAH is associated with other diseases, such as connective tissue disease or HIV. Others develop PAH after a long-term response to calcium channel blockers. Five to 10% of patients with PAH have pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. Finally, a small percentage of patients have PAH at birth, the authors said.

In addition to dyspnea and fatigue, patients often report lower extremity edema or heart palpitations. While an echocardiogram can be a good first step toward diagnosis, investigators said the condition can only be diagnosed with right heart catheterization, a procedure they say has a low risk of complications.

In terms of treatment, the authors said currently available treatments include drugs designed to enhance the nitric oxide and cyclic guanosine monophosphate pathway, prostacyclin agonists, and endothelin pathway agonists. These include sildenafil (Viagra), epoprostenol (Flolan), and bosentan (Tracleer), among others. These therapies have helped increase the 5-year survival rate in patients with PAH from just 1 in 3 in 1991 to 60% in 2015, the researchers noted.

Adjuvant treatments, such as diuretics and aldosterone agonists, are commonly used in patients with PAH. Oxygen therapy is also recommended for patients whose PaO2 levels remain consistently below 60 mm Hg, the authors noted.

One point doctors should keep in mind, they concluded, is that women who are pregnant and have PAH are at high risk of ventricular failure and death due to PAH-related cardiac changes. They said women with PAH should avoid birth control containing estrogen, as it can increase the risk of thromboembolism.


Ruopp NF, Cockrill BA. Diagnosis and treatment of pulmonary arterial hypertension: a review. JAMA. 2022;327(14):1379-1391. doi:10.1001/jama.2022.4402


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