Causes and Diagnoses

Causes and Diagnoses of Pulmonary Hypertension

Pulmonary hypertension (PH) can be caused by many different heart and lung disorders. PH refers to pulmonary hypertension from any cause. Pulmonary arterial hypertension (PAH) refers to a form of PH that starts in the arteries of the lung. PAH can be associated with any number of other conditions, or can occur in isolation, where it is referred to as idiopathic pulmonary arterial hypertension (IPAH).

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Causes/Risk Factors

People of all ages, races and ethnic backgrounds are diagnosed with PH. Even though anyone can be diagnosed with PH, certain risk factors make some people more likely to get the disease. Following are some known risk factors:

  • Family history: If two or more members of your family have PH or if a family member in your lineage is known to have a PH-causing gene mutation, the risk of getting PH is more likely. Genetic counseling is available to discuss these issues.
  • Obesity and obstructive sleep apnea: In isolation, obesity is not a risk factor. However, if obesity is combined with obstructive sleep apnea (meaning that oxygen levels fall while a person is sleeping), mild PH may occur.
  • Gender: IPAH 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: According to expert opinion, pregnancy is a possible risk factor. Women who have been diagnosed with PH and become pregnant must be monitored closely.
  • Altitude: Living at a high altitude for years can make your risk of being diagnosed with PH greater. When travelling to high altitudes, PH symptoms can become worse.
  • Drugs and toxins: Certain drugs, such as methamphetamines and the diet drug “fen phen,” are known to cause PH.

Connective tissue disorders
All of the connective tissue disorders (also known as collagen vascular disease) may be associated with PH. These include:

  • CREST syndrome and scleroderma
  • Systemic lupus erythematosus
  • Sjögren’s syndrome
  • Dermatomyositis
  • Polymyositis
  • Rheumatoid arthritis

Some patient may be unaware that they have a connective tissue disease, which may be discovered from a blood test. Treatment of these patients is identical to that of patients with IPAH but is often less effective. The treatment of the PH, however, does not affect the natural history of the underlying connective tissue disease.

Congenital Cardiac Shunts
Babies born with a “hole in the heart”, or with abnormal vessels may have PH from birth. In some instances it can be severe and is diagnosed readily. In these cases surgery is often necessary to correct the problem. The most common congenital abnormality, an atrial septal defect (ASD) can be very mild and is often missed even though the child has annual exams. There may be no symptoms in the younger years. The condition often becomes apparent when the patient is an adult. Some patients have corrective surgery but develop PH years or even decades after surgical correction. These patients present similarly to patients with IPAH but tend to have a better long-term survival. The treatments are similar to those for IPAH.

Portal Hypertension
Patients with advanced liver disease can develop high pressure in the veins of the liver, known as portal hypertension. Portal hypertension is associated with PH, but the mechanism remains unknown. Patients with advanced cirrhosis can have the combined features of their liver disease in association with the features of PH, which can be difficult to separate. Patients with mild PH who have a favorable response to medical treatments have undergone successful liver transplantation with improvement of the pulmonary vascular disease.

Left Heart Diastolic Dysfunction
PH occurs as a result of increased resistance to blood flowing from the pulmonary veins into the left side of the heart. The most common cause of PH seen today is referred to as “left heart diastolic dysfunction,” but it can also be associated with heart valve problems. Left heart diastolic dysfunction may be associated with obesity, diabetes, high blood pressure and aging. One distinctive symptom of left heart diastolic dysfunction is difficulty breathing when lying flat. Clinically it may be confusing and appear as if two separate disease processes are occurring simultaneously. The distinction is important, however, as some of the treatments that are effective in PAH may make patients with left heart diastolic dysfunction worse. There are no specific treatments available to treat left heart diastolic dysfunction, but several clinical trials are underway.

Chronic Obstructive Lung Disease
Chronic obstructive lung disease (COPD) and emphysema are often associated with mild PH in the advanced stages. A subgroup of these patients may have severe PH. The presence of PH in patients with COPD is associated with a worse outcome. The only effective therapy is supplemental oxygen. The COPD will also need to be treated which typically will require inhaled therapies. Long-term oxygen therapy is indicated in patients whose oxygen levels fall when they walk.

Interstitial Lung Disease
Mild PH is common in interstitial lung disease (scarring of the lung), which can be caused by many illnesses. The cause of the interstitial lung disease should be found. Some patients have a condition known as pulmonary fibrosis for which no known cause can be found. Patients are commonly older than 50 years and report a gradual onset of progressive breathlessness and cough for months to years. The pulmonary vasodilators approved for PAH have not been shown to be helpful.

Obstructive Sleep Apnea
The incidence of PH in the setting of obstructive sleep apnea, a common condition, is less than 20 percent and is generally mild. Some patients have severe PH in conjunction with sleep apnea, which may be unrelated. It is recommended that the sleep apnea and the PH be treated as coexisting problems.

Chronic Thromboembolic Pulmonary Hypertension
Pulmonary thromboembolism (blood clot in the lung) is a common condition and can occur in otherwise healthy individuals. Some patients may have an underlying predisposition to forming blood clots as well.  Most patients treated for acute pulmonary thromboembolism with anticoagulants (blood thinners) do not develop chronic PH. However, some patients have impaired ability to dissolve the clots, which leads to chronic obstruction of the pulmonary arteries and PH. Because the initial pulmonary thromboembolism may go undetected or untreated, many of these patients are misdiagnosed with PAH. This is the only potentially curable form of PH. Pulmonary endarterectomy (PEA) is an operation where the clots are surgically removed, which restores the blood flow and lowers the pulmonary artery pressures. With successful surgery, patients often recover to a point that they no longer have any symptoms and live without related problems for decades.

Sarcoidosis (a disease that causes scarring in many organs of the body) can produce PH as a result of fibrosis of the lung or direct involvement of the pulmonary arteries. Consequently, patients with sarcoidosis who present with progressive breathlessness and PH need a thorough evaluation. There is a subset of patients with sarcoidosis and severe PH that exhibit a favorable response to approved therapies.

Sickle Cell Disease
Sickle cell disease can involve the heart and lung in a wide variety of ways, including high blood pressure, low oxygen, thromboembolism, chronic anemia and chronic liver disease. The presence of PH in patients with sickle cell disease is associated with a higher rate of death. Intensification of sickle cell disease specific therapy appears to be helpful. Approved drugs for PAH are not generally effective in this condition.

HIV Infection
The mechanism by which HIV infection produces PH remains unknown. The incidence is estimated at 1 out of every 200 cases of HIV will be affected with PH. The evaluation and treatments are identical to those for PAH. Treatment of the HIV infection does not appear to affect the severity or natural history of the underlying PH.

Diagnosis of Pulmonary Hypertension

PH is rarely discovered in a routine medical exam. In its later stages, the signs of the disease can be confused with other conditions affecting the heart and lungs. Before treatment for PH begins, it is essential that a correct diagnosis of the cause for PH be established. Recent studies have shown that over half of the patients with PH are initially misdiagnosed.

To determine if you have PH and what type, your medical team will schedule specialized tests. If your medical team suspects PH as a result of one or more of the following tests, they will go on to schedule a heart catheterization, which is required to confirm diagnosis.

Blood Tests
Blood tests check the oxygen levels in the blood, observe liver and kidney function, identify collagen vascular disease, thyroid problems, signs of infection or HIV antibodies. The brain natriuretic peptide blood test helps to assess the strain on the heart and may also be used to monitor how patients are responding to treatment.

Chest X-rays
Chest X-rays can reveal, specific to PH, an enlarged right ventricle or pulmonary arteries. Chest X-rays can also show signs of emphysema or scarring (interstitial fibrosis) of the lungs and if there is fluid in the lungs.

Electrocardiogram (ECG)
An electrocardiogram checks the electrical impulses of the heart. Electrodes are attached to the patient's skin, and a recording of these impulses is made. Some patients may develop abnormal heart rhythms from PH, which can worsen their symptoms.

An Echocardiogram is an ultrasound test that produces a “moving” picture of the heart. These pictures show the condition of the heart muscle, heart valves and check for congenital abnormalities. This painless test is often used to make a preliminary diagnosis of PH by estimating the pressures in the right heart and assessing how well the heart is functioning. Other heart conditions that produce symptoms similar to PH may be diagnosed with an echocardiogram.

Pulmonary Function Tests
These tests measure the mechanics of how you breathe, how much air your lungs can hold, how much air moves in and out of them and the lungs’ ability to exchange oxygen. These tests can potentially identify the cause of PH when a lung problem is believed to exist. Some patients can have PH associated with a problem of the lung and of the heart together.

Nuclear Scan (Ventilation/Perfusion Scan or V/Q Scan)
This diagnostic tool tests for blood clots in the lungs by producing a picture of air and blood flow to the lungs. A small dose of radioactive material is breathed in and another small dose is injected via a blood vessel into the lungs. It is considered the best screening test to look for blood clots. A completely normal scan effectively excludes clots in the lungs.

Chest CT (CAT) Scanning  
A computerized axial tomography scan (CT scan), a precise imaging technique of the body, provides more detailed images than a chest X-ray, and is performed in a specialized X-ray machine that takes pictures that create cross sectional images (or slices) of your body. A chest CT scan is used to examine the heart and lungs in detail. It may reveal underlying disease of the lung tissue or the chest structures. It may also be used to look for blood clots in the lungs. 

Cardiac MRI (magnetic resonance imaging)
A cardiac magnetic resonance imaging test (cardiac MRI) is a special non-X-ray imaging technique that, among other uses, can accurately measure right heart chamber volumes and function. It provides the most precise measurements available of how the heart is responding to the PH. Certain devices such as pacemakers may not be compatible with MRI testing due to the magnetic field generated during the scan.

Exercise Testing
Several types of exercise tests are used to measure how limited, physically, someone is by their PH. The specific test your physician orders may depend on what type of problem you appear to have or how sick you are. The different exercise tests include:

  • 6-Minute Walk Test: measures how far a person can walk in 6 minutes; used to provide an estimate of exercise capacity
  • Treadmill Test: measures how long a person can walk on a treadmill with increasing speed and incline; a more formalized way to determine exercise capacity
  • Cardiopulmonary Exercise Testing: the most sophisticated way to measure heart and lung function; often performed when there is uncertainty about the nature of a person’s breathlessness

Cardiac (Heart) Catheterization
If the results of initial testing points to a diagnosis of PH, your doctor will schedule a heart catheterization. This test will usually include a study of the left side (left heart catheterization) and right side (right heart catheterization) of the heart. This is the only test that directly measures the pressure inside the heart and pulmonary arteries and it should be done in all patients to confirm a diagnosis of PH. Heart catheterization is one of the most accurate and useful tests to confirm a diagnosis for PH.

During the test, doctors insert a catheter (a thin plastic tube) through a large vein in the patient's groin or neck. They then pass the catheter up into the patient's heart to measure the blood pressure in the right side of the heart and lungs. With a right heart catheter in place, the patient may be given drugs that relax the pulmonary arteries. The test drug is given to the patient in higher and higher doses, pausing at each dose to see how the patient reacts. Once a significant response occurs or the side effects become intolerable, the test is considered complete. A second catheter may be placed in a large artery from the groin, which is passed into the left heart. Measurement of the pressure inside the left heart is of critical importance. If there is a reason to believe a patient may have blockages in the arteries of the heart, the doctors will be able to take pictures of the arteries of the heart (coronary arteries) at the same time.

Related Resources

Pulmonary Hypertension: Pulmonary hypertension can occur in children and adults. Learn more about the causes and symptoms.