Pulmonary Hypertension

PAH is a chronic and currently incurable disease that causes the walls of the arteries of the lungs to tighten and stiffen, increasing blood pressure. In someone with PAH, the right side of the heart has to work harder to push blood through narrowed arteries in the lungs.² Eventually, the extra stress causes the heart to enlarge and become less flexible, compromising the heart's ability to push blood out and into the lungs and the rest of the body.¹ In idiopathic PAH, the cause of the disease is unknown.³ Heritable PAH is acquired genetically.⁴ In associated PAH, patients with other conditions (eg, scleroderma, congenital heart disease, lupus, or HIV) have the disease.^1,5 A rare form of PAH, chronic thromboembolic pulmonary hypertension (CTEPH), is caused by old blood clots in the lungs.⁶

PAH is a rare disease affecting 15 to 50 cases per million.⁷ Its prevalence is higher in certain groups of patients suffering from other diseases.⁸ For instance, in patients with sickle cell disease, the prevalence is around 2% to 3.75%.⁹ PAH affects people of all ages, races, and ethnic backgrounds.¹ Although anyone can get PAH, the following risk factors can make some people more susceptible.^1,10,11

• Family history: If two or more family members have PAH, or if a family member is known to have a PAH-causing gene mutation, the risk of getting PAH is higher. Genetic counseling is available to discuss these issues
• Obesity and obstructive sleep apnea: On its own, obesity is not a risk factor. However, if it is combined with obstructive sleep apnea, mild PAH may occur
• Gender: Idiopathic PAH and heritable PAH (also known as familial PAH) are at least two and a half times more common in women than in men. Females of childbearing age are also more susceptible
• Pregnancy: Pregnancy may be a risk factor. Women who already have PAH and become pregnant have a much higher risk of mortality
• Altitude: Living at a high altitude for years can predispose individuals to PAH. When patients travel to regions with high altitudes, their PAH symptoms may worsen
• Other diseases: Other diseases, including congenital heart disease, lung disease, liver disease, and connective tissue diseases like scleroderma and lupus, can lead to the development of pulmonary hypertension
• Drugs and toxins: Use of certain drugs, such as methamphetamines and the diet drug, “fen phen” has been known to cause pulmonary hypertension

Patients experience symptoms such as shortness of breath, dizziness, and fatigue, and the severity of symptoms usually correlates with the progression of the disease.¹

Other symptoms may include:^1,11

• Chest pain (angina pectoris)
• Dizziness
• Fainting (syncope)
• Loss of energy
• Swelling of the arms, legs, ankles, or abdomen (edema)
• Dry cough
• Raynaud’s phenomenon (chalky white or dusky blue fingers that may be painful and can sometimes be provoked by the cold)

In advanced stages of pulmonary hypertension, minimal activity may produce some or all of these symptoms. Patients in advanced stages may experience irregular heartbeat, a racing pulse, passing out, and difficulty breathing when at rest.¹

There are a number of different ways to diagnose PAH. Blood tests may be used to check oxygen levels and liver and kidney function and to identify the presence of collagen vascular disease, thyroid problems, signs of infection, or HIV antibodies.^10,11,12

One test can check for levels of brain natriuretic peptide to assess the strain on the heart and monitor response to treatment. In addition, chest X-rays can be used to check the right ventricle of the heart and the pulmonary arteries for signs of enlargement. They can also reveal the presence of emphysema or scarring (interstitial fibrosis) of the lungs. An electrocardiogram or echocardiogram may also be used to monitor heart function.¹⁰

To focus on the lungs, pulmonary function tests measure oxygen capacity in the lungs and their ability to exchange oxygen. A nuclear scan (also called a ventilation/perfusion, or V/Q, scan) tests for blood clots in the lungs by producing a picture of air and blood flow to the lungs.¹⁰ With this test, the patient inhales a small dose of radioactive marker, while another small dose is injected into a blood vessel, to allow imaging of the lungs. The resulting images give doctors an idea of lung health.¹³

In addition, a six-minute stress test may be required to show the patient's tolerance for exercise.¹⁴

One of the most definitive diagnostic tests for PAH is right-heart catheterization, which directly measures the pressure inside the patient's pulmonary arteries. It should be performed at least once in any patient who might have PAH. During the test, doctors insert a thin rubber tube, or catheter, through a large vein in the patient's groin or neck. They then pass the catheter up into the patient's heart to measure blood pressure in the right side of the heart and lungs.¹⁵

A vasodilator study is required for patients who have been diagnosed with PAH to determine how much their pulmonary blood vessels can relax over a brief period of time. Its main purpose is to screen for patients who might respond favorably to treatment with calcium channel blockers. The test can also help determine the patient's prognosis. With a right-heart catheter in place, the patient is given drugs that relax the pulmonary arteries. The test drug is given to the patient in higher and higher doses, pausing after each dose to see how the patient reacts. Once a significant response occurs, or the side effects become intolerable, the test is considered complete.¹⁶

While there is currently no cure for PAH, different treatment options are available to help manage the disease and help patients feel better day to day. Conventional therapies include treatment with calcium channel blockers, which can help lower blood pressure; digoxin, which can help improve heart pumping; diuretics, which eliminate excess fluid that might put more pressure on the heart; oxygen, to help with breathing; the blood thinner warfarin to prevent clotting; endothelin receptor agonists, to help prevent blood vessels from constricting; and phosphodiesterase and soluble guanylate cyclase inhibitors, which allow the lungs to generate natural vasodilators to relieve blood vessel constriction. Prostacyclins may also be used to help relieve shortness of breath.^1,11,17

Experimental treatments may be available to patients who take part in clinical trials. When the disease is very advanced and resists treatment, lung transplants may be recommended.¹⁸ It is important to seek treatment from specialists in PAH, and physicians should include cardiologists, pulmonologists, and rheumatologists. Nurses, pharmacists, and internists may also have special training in pulmonary hypertension. Most generalists lack sufficient training or experience with PAH, so patients should always see PAH specialists.