What Is Pulmonary Arterial Hypertension?

Pulmonary (PULL-mun-ary) arterial hypertension (PAH) is continuous high blood pressure in the pulmonary artery. The average blood pressure in a normal pulmonary artery is about 14 mmHg when the person is resting. In PAH, the average is usually greater than 25 mmHg.

PAH is a serious condition for which there are treatments but no cure. Treatment benefits many patients.

The pulmonary arteries are the blood vessels that carry oxygen-poor blood from the right ventricle (VEN-trih-kul) in the heart to the small arteries in the lungs. In PAH, three types of changes may occur in the pulmonary arteries:

• The muscles within the walls of the arteries may tighten up. This makes the inside of the arteries narrower.
• The walls of the pulmonary arteries may thicken as the amount of muscle increases in some arteries. Scar tissue may form in the walls of arteries. As the walls thicken and scar, the arteries become increasingly narrow.
• Tiny blood clots may form within the smaller arteries, causing blockages.

There is less room for the blood to flow through these narrower arteries. The arteries may also stiffen. Over time, some of the arteries may become completely blocked.

The narrowing of the pulmonary arteries causes the right side of heart to work harder to pump blood through the lungs. Over time, the heart muscle weakens and loses its ability to pump enough blood for the body's needs. This is called right heart failure. Heart failure is the most common cause of death in people with PAH.

There are two types of PAH:

• Primary pulmonary arterial hypertension (PPAH) is inherited or occurs for no known reason.
• Secondary pulmonary arterial hypertension (SPAH) either is caused by or occurs because of another condition. The conditions include chronic heart or lung disease, blood clots in the lungs, or a disease like scleroderma (skler-o-DER-ma).

About 300 new cases of PPAH are diagnosed in the United States each year. SPAH is much more common.

Doctors have learned a lot about PAH in recent years. More treatments are now available. Researchers are also studying several promising new treatments that may prolong lives as well as improve the quality of life for people living with PAH.

Other Names for Pulmonary Arterial Hypertension

• Idiopathic pulmonary arterial hypertension
• Sporadic primary pulmonary hypertension
• Familial primary pulmonary hypertension
• Secondary pulmonary arterial hypertension
• Pulmonary hypertension

What Causes Pulmonary Arterial Hypertension?

Certain factors appear to increase your chances of developing pulmonary arterial hypertension (PAH). They include:

• Use of appetite suppressants, especially fenfluramine (fen-FLOO-ra-men) and dexfenfluramine (deks-fen-FLOO-ra-men)
• Chronic use of cocaine or amphetamines
• HIV infection
• Liver disease
• Connective tissue diseases, such as scleroderma or lupus erythematosus

Doctors do not know what causes primary pulmonary arterial hypertension (PPAH), although it is inherited in some people. Recently, researchers discovered a defect in a gene that can lead to changes in the pulmonary arteries like those seen in PPAH. They think that other genes may be involved as well. As we learn more about how different genes work in the development of PPAH, better treatments and perhaps a preventive treatment or cure will be found.

Secondary pulmonary arterial hypertension (SPAH) is caused by a variety of conditions. Chronic obstructive pulmonary disease is the most common cause in adults.

Other Conditions That Can Lead to SPAH

• Obstructive sleep apnea
• Congenital heart defects
• Chronic blood clots in the pulmonary artery

PAH affects men and women of all ages, from very young children to seniors, and people of all racial and ethnic backgrounds.

PPAH is most common in women in their thirties and men in their forties. Twice as many cases are reported in women as in men.

What Are the Signs and Symptoms of Pulmonary Arterial Hypertension?

Difficulty breathing or shortness of breath (dyspnea) is the main symptom of pulmonary arterial hypertension (PAH). If you have PAH, you may feel that it is difficult to get enough air.

Other Common Signs and Symptoms

• Fatigue
• Dizziness
• Fainting spells (syncope)
• Swelling in the ankles or legs (edema)
• Bluish lips and skin (cyanosis)
• Chest pain
• Racing pulse
• Palpitations (a strong feeling of a fast heartbeat)

As the disease advances:

• The pumping action of your heart grows weaker.
• Your energy decreases.

In the more advanced stages, you:

• Are able to perform very little activity
• Have symptoms even when resting
• May become completely bedridden

Limitations on Physical Activity

Doctors may classify your symptoms based on how much activity you can comfortably undertake. The classes are the same as those for heart failure. They are:

• Class 1: No limits—Ordinary physical activity does not cause undue tiredness or shortness of breath.
• Class 2: Slight or mild limits—Person is comfortable at rest, but ordinary physical activity results in tiredness or shortness of breath.
• Class 3: Marked or noticeable limits—Person is comfortable at rest, but less than ordinary physical activity causes tiredness or shortness of breath.
• Class 4: Severe limits—Person is unable to carry on any physical activity without discomfort. Symptoms may also be present at rest. If any physical activity is undertaken, discomfort increases.

How Is Pulmonary Arterial Hypertension Diagnosed?

There is no one specific test that will show why you have pulmonary arterial hypertension (PAH). Even in its later stages, the signs of the disease are similar to those of other heart and lung conditions.

Your doctor will determine if you have PAH by conducting a series of tests to:

• Determine the pressure in your pulmonary artery
• Find out how well your heart and lungs are working
• Rule out any other conditions that may be causing the hypertension

These tests include:

• Chest x ray. A chest x ray takes a picture of your heart and lungs. It can show if the pulmonary arteries or the right side of the heart are enlarged. It will also help your doctor rule out a number of lung diseases, including chronic obstructive pulmonary disease (COPD), as the cause of your PAH.
• EKG (electrocardiogram). This test is used to measure the rate and regularity of your heartbeat, as well as the size and position of the right ventricle in your heart. It can help the doctor rule out a number of diseases of the heart.
• Echocardiogram. This test uses sound waves to create a moving picture of your heart. Echocardiogram provides information about the size and shape of your heart and how well your heart chambers and valves are functioning. The test also can identify areas of poor blood flow to the heart, areas of heart muscle that are not contracting normally, and previous injury to the heart muscle caused by poor blood flow.
• There are several different types of echocardiograms, including a stress echocardiogram. During this test, an echocardiogram is done both before and after your heart is stressed either by having you exercise or by injecting a medicine into your bloodstream that makes your heart beat faster and work harder. A stress echocardiogram is usually done to find out if you have decreased blood flow to your heart (coronary artery disease).
• Stress Test. Some heart problems are easier to diagnose when your heart is working harder and beating faster than when it’s at rest. During stress testing, you exercise (or are given medicine if you are unable to exercise) to make your heart work harder and beat faster while heart tests are performed.
• During exercise stress testing, your blood pressure and EKG readings are monitored while you walk or run on a treadmill or pedal a bicycle. Other heart tests, such as nuclear heart scanning or echocardiography, also can be done at the same time. These would be ordered if your doctor needs more information than the exercise stress test can provide about how well your heart is working.
• If you are unable to exercise, a medicine can be injected through an intravenous line (IV) into your bloodstream to make your heart work harder and beat faster, as if you are exercising on a treadmill or bicycle. Nuclear heart scanning or echocardiography is then usually done.
• During nuclear heart scanning, radioactive tracer is injected into your bloodstream, and a special camera shows the flow of blood through your heart and arteries. Echocardiography uses sound waves to show blood flow through the chambers and valves of your heart and to show the strength of your heart muscle.
• Your doctor also may order two newer tests along with stress testing if more information is needed about how well your heart works. These new tests are magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning of the heart. MRI shows detailed images of the structures and beating of your heart, which may help your doctor better assess if parts of your heart are weak or damaged. PET scanning shows the level of chemical activity in different areas of your heart. This can help your doctor determine if enough blood is flowing to the areas of your heart. A PET scan can show decreased blood flow caused by disease or damaged muscles that may not be detected by other scanning methods.
• Spirometry (spi-ROM-e-tre). This test measures how well your lungs inhale and exhale air. It is most useful for ruling out obstructive lung diseases like COPD.
• Cardiac catheterization. This test provides a precise measure of the blood pressure in the right side of your heart and the pulmonary artery. Cardiac catheterization is the only way to get this measure. It also shows the amount of blood the right ventricle pumps with each heartbeat. This helps your doctor evaluate the pumping ability of the right ventricle. This procedure must be performed in the hospital by a specialist.

Usually, these tests are sufficient to confirm that you have PAH. Sometimes these tests do not rule out all possible causes for the PAH. In that case, your doctor may call for these additional tests:

• Perfusion lung scan. This test shows how the blood is moving in your lungs and whether there are large blood clots that may be causing the PAH.
• Pulmonary arteriography. When the results of a perfusion lung scan do not rule out blood clots in the pulmonary arteries, your doctor may order a pulmonary arteriogram. This test also shows blood clots and other blockages in the blood vessels in the lung.
• Blood tests. Blood tests will rule out HIV, auto-immune diseases like scleroderma, and liver disease.
• Polysomnography (POL-e-som-NOG-ra-fe). This test will help your doctor rule out sleep-disordered breathing as a cause of your PAH.

If these tests do not show an underlying cause for the PAH, the diagnosis is primary pulmonary arterial hypertension.

How Is Pulmonary Arterial Hypertension Treated?

The goals of treatment for patients with pulmonary arterial hypertension (PAH) are to:

• Treat the underlying cause. This is the first priority in patients with secondary pulmonary arterial hypertension (SPAH). Sometimes this treatment can correct the PAH.
• Reduce symptoms and improve quality of life.
• Slow the growth of the smooth muscle cells and the development of blood clots.
• Increase the supply of blood and oxygen to the heart, while reducing its workload.

These treatments include:

• Medicines
• Oxygen
• Lung transplantation

Medicines

• Anticoagulants (AN-te-ko-AG-u-lants) reduce the formation of blood clots.
• Calcium channel blockers relax blood vessels and increase the supply of blood and oxygen to the heart, while reducing its workload. These drugs can be very helpful, but only for a small amount of patients. All patients that take them should be monitored carefully.
• Epoprostenol (e-poe-PROST-en-ole) is a type of medicine called a prostacyclin (pros-ta-SI-klin). It is currently considered the most effective therapy for primary pulmonary arterial hypertension (PPAH). It may also be helpful in treating some forms of severe SPAH. This medication widens the lung arteries and prevents blood clot formation. Until recently, it was given intravenously through a permanent tube, or catheter, placed in a vein in the neck and connected to a battery-powered pump. But in December 2004, a new form of the drug, iloprost, was approved for the treatment of PAH. This medicine can be inhaled through a nebulizer. This makes it more convenient and less painful to take. Plus the medicine goes directly to the lungs, where it is needed.
• Treprostinil, another prostacyclin, also relaxes blood vessels and increases the supply of blood to the lungs, reducing the workload of the heart. It can be given under the skin.
• Bosentan, a relatively new treatment, widens the lung arteries and reduces blood pressure. It also is available in pill form. Until doctors learn more about the long-term effects, all patients taking this drug should be monitored for complications, especially those involving the liver.
• Nitric oxide inhalation, which causes the pulmonary arteries to widen or open, is also being used by some doctors.
• Sildenafil (Viagra®), another drug that causes the pulmonary arteries to open, has recently been shown to improve the condition of PAH patients and is expected to be approved soon. This drug is available in pill form.
• Diuretics (water or fluid pills) may help ease symptoms and improve the heart's performance in some patients with PAH.

Oxygen

You may need oxygen therapy if the level of oxygen in your blood is low. Oxygen is usually given through nasal prongs or a mask. Over time, you may need oxygen around the clock.

Lung Transplantation

Surgery to replace one or both diseased lungs with healthy lungs from a human donor may help some patients. This procedure is usually recommended for patients for whom medical therapy is no longer effective. Complications include rejection by the body of the transplanted lung and infection. Transplant patients must take medicines for life to reduce the chances that their body will reject the transplanted lung.

Other Possible Treatments

Researchers also are studying whether stem cell transplantation combined with gene therapy may provide a cure for PAH in the not too distant future.

Living With Pulmonary Arterial Hypertension

Many people with pulmonary arterial hypertension (PAH) do not look sick. Many feel perfectly well most of the time, as long as they do not strain themselves physically. In the early stages of the disease, many are able to go to school or work on a full- or part-time basis.

Relaxation exercises and stress reduction activities may help many people with PAH keep up with their regular activities for a while. Having a positive attitude is also helpful.

Walking is good exercise for many people with PAH. Advanced patients who find walking too exhausting may use a wheelchair or motorized scooter. Others stay busy with activities that are not of a physical nature.

Some people with advanced PAH carry portable oxygen when they go out.

Ongoing medical care is important. Treatment by a cardiologist or pulmonologist (pull-mon-OL-o-gist) who specializes in pulmonary vascular medicine is usually recommended. These specialists are usually located at major medical centers.

PAH patients should also eat a healthy diet and get plenty of rest, and they should not smoke.

Situations that can make PAH symptoms worse are:

• Living at high altitudes or traveling to high-altitude areas where the air is thin and the amount of oxygen in the air is low
• Air travel
• Pregnancy

Key Points

• Pulmonary arterial hypertension (PAH) is high blood pressure in the pulmonary arteries in the lungs.
• In PAH, the small arteries in the lungs narrow and may eventually become blocked. As a result, the heart must work harder to pump the blood through them. Over time, the overworked heart muscle becomes weak and loses its ability to pump enough blood to the lungs.
• PAH is called primary pulmonary arterial hypertension (PPAH) when no cause can be found for it. Secondary pulmonary arterial hypertension (SPAH) refers to PAH that is caused by or occurs with another condition—usually heart or lung disease.
• Certain factors appear to increase your chances of developing PAH, including use of appetite suppressants or cocaine and the presence of other diseases like HIV infection, scleroderma, and liver disease.
• PPAH may be caused by an abnormality in a gene.
• Common symptoms of PAH include difficulty breathing, fatigue, dizziness, fainting spells, swelling in the ankles or legs, bluish lips and skin, chest pain, and palpitations.
• PAH often is not diagnosed right away because its symptoms are similar to those of other conditions affecting the heart and lungs, and those conditions must be ruled out. Tests that can help confirm a PAH diagnosis include electrocardiogram, echocardiogram, pulmonary function tests, and cardiac catheterization.
• Right heart catheterization is the only way to obtain a precise measure of the blood pressure in the right side of the heart and the pulmonary artery. It is necessary to confirm suspected PPAH.
• Treatments for PAH include anticoagulants, calcium channel blockers, continuous intravenous epoprostenol (prostacyclin and other forms of prostacyclin), new drugs (Bosentan), and sildenafil.
• Surgery to replace one or both diseased lungs with healthy lungs from a human donor can help some people with PAH.
• Relaxation exercises, stress reduction activities, and adoption of a positive attitude can help PAH patients keep up with their normal activities. Eating a healthy diet, getting plenty of rest, and not smoking are also beneficial.
• Ongoing medical care, usually by a cardiologist or pulmonologist who specializes in pulmonary vascular medicine, is important.

Links to Other Information About Pulmonary Arterial Hypertension

NHLBI Resources

• NHLBI-Related Public Interest Organizations
• Lung Diseases Information for the Public

Non-NHLBI Resources

• Pulmonary Hypertension (MedlinePlus)

Clinical Trials

• Current Research (ClinicalTrials.gov)