BALTIMORE — The incidence of pulmonary arterial hypertension is widely underestimated, but with better diagnostic tools and more treatments, rheumatologists and others can intervene earlier in the disease process, said Dr. Hunter Champion at a cardiovascular conference sponsored by Johns Hopkins University, Baltimore.
There are 1–2 million cases of pulmonary arterial hypertension (PAH) a year, primarily affecting women and usually striking people in their 40s. But PAH is on the rise, said Dr. Champion of the university.
Hospitalizations for PAH tripled from 1980 to 2002, when they hit 260,000, according to the National Hospital Discharge Survey (www.cdc.gov/mmwr/preview/mmwrhtml/ss5405a1.htm#tab10
Suspect PAH if there is a loud pulmonic closure, right ventricular lift, systolic murmur (tricuspid regurgitation), diastolic murmur (pulmonary regurgitation), or right ventricular presystolic gallop. A family history of PAH, connective tissue disease, congenital heart disease, portal hypertension, a history of deep vein thrombosis or pulmonary embolism, human immunodeficiency virus, and appetite-suppressant use are all risk factors, Dr. Champion said.
Symptoms usually include dyspnea, angina, syncope, edema, and Raynaud's phenomenon. PAH is often misdiagnosed as coronary artery disease (CAD), heart rhythm disorder, asthma, or, sometimes, a psychiatric condition such as panic disorder, he said.
Diagnostics should be done to rule out HIV, emphysema, sleep disorder, CAD, and autoantibody disorders such as systemic lupus erythematosus.
A right heart catheterization is critical, he said. “Until you have that, you don't really have a handle on what's going on.”
The catheterization also will give a reading on pulmonary artery pressure and response to vasodilators, both of which help determine a therapeutic strategy.
PAH arises through the endothelin, nitric oxide, and prostacyclin pathways. Three prostacyclin analogues are the most commonly used therapies: epoprostenol (Flolan), treprostinil (Remodulin), and iloprost (Ventavis). The drugs are expensive—$60,000–$100,000 a year—and have drawbacks, including jaw, leg, and site pain (for epoprostenol, which is delivered through an in-dwelling catheter), and risk of infection and thrombocytopenia. With epoprostenol, rebound PAH is common, he said.
Bosentan (Tracleer) acts on the endothelin pathway. The oral medication has been shown to delay PAH progression, although it is still considered palliative. It has a high risk of teratogenicity, which is important to consider because many PAH patients are women in their childbearing years.
Liver damage is also a continuing concern. The Food and Drug Administration recently strengthened hepatotoxicity warnings and emphasized the need to conduct monthly liver function tests. Bosentan is also expensive: $36,000 a year.
Two new therapies are considered promising for treating PAH, they include Sitaxsentan, which was recently designated as approvable by the FDA, and ambrisentan, which is close to market. Both are type-A selective endothelin receptor antagonists.
Sildenafil (Viagra) has been shown to improve patient functioning, as demonstrated by the 6-minute walking test. Dr. Champion said he was impressed with the drug's ability to convert patients from class IV to class III status or from class III to class II. The phosphodiesterase 5 inhibitor is marketed as Revatio for PAH. It is the lowest-priced therapy, at about $9,800 a year.
Lung transplantation is a possibility for advanced PAH, but a recent change in United Network for Organ Sharing rules has lengthened patients' wait, Dr. Champion said. “It is the option of last resort but certainly is necessary,” he said.