- Risk Factors
- Signs & Symptoms
Pulmonary hypertension definition and facts
- Pulmonary hypertension is abnormally elevated pressure in the pulmonary circulation.
- The classification of primary and secondary pulmonary hypertension has been reclassified and now is based on the main underlying disease or condition, symptoms, and treatment options for pulmonary hypertension. There are five classes or groups in this new classification system.
- Pulmonary hypertension can have no identifiable cause and is then referred to as idiopathic pulmonary hypertension (formerly called primary pulmonary hypertension).
- Pulmonary hypertension can be caused by certain drugs, diseases (scleroderma, dermatomyositis, systemic lupus), infections (HIV, schistosomiasis), liver disease, valvular heart disease, congenital heart disease, chronic obstructive lung disease (COPD), blood clots in the lungs, and persistent pulmonary hypertension of the newborn (PPHN).
- Risk factors for pulmonary hypertension are liver failure, chronic lung disease, blood clotting disorders, and underlying diseases, such as scleroderma, dermatomyositis, and systemic lupus erythematosus.
- Signs and symptoms of pulmonary hypertension include:
- shortness of breath,
- difficulty breathing with exertion,
- rapid breathing, and
- rapid heart rate.
- Pulmonary hypertension is diagnosed by measuring the pulmonary pressures by either ultrasound of the heart (echocardiogram) or right heart catheterization.
- The treatment for pulmonary hypertension can include oxygen, diuretics, blood thinners, medications that open the pulmonary arteries, and treatments for any underlying disease.
- The prognosis and life expectancy for a person with pulmonary hypertension is improving as newer treatment options become available; however, the prognosis may depend on the underlying disease or condition that is causing pulmonary hypertension.
What is pulmonary hypertension?
Pulmonary hypertension occurs when the pressure in the pulmonary arteries increases abnormally. To help explain this condition further, here is how the pulmonary arteries work.
What are pulmonary arteries?
The human body has two major sets of blood vessels that distribute blood from the heart to the body. One set pumps blood from the right heart to the lungs, and the other from the left heart to the rest of the body (systemic circulation). When a doctor or a nurse measures the blood pressure on a person's arm, he/she is measuring the pressures in the systemic circulation. When these pressures are abnormally high, the person is diagnosed as having high blood pressure (systemic hypertension).
The portion of the circulation that distributes the blood from the right side of the heart to the lungs and back to the left side of the heart is referred to as pulmonary (lung) circulation.
The right ventricle pumps the blood returning from the body into the pulmonary arteries to the lungs to receive oxygen. The pressures in the lung arteries (pulmonary arteries) are normally significantly lower than the pressures in the systemic circulation. When the pressure in the pulmonary circulation becomes abnormally elevated, it is referred to as pulmonary hypertension. This most commonly occurs when the pulmonary venous pressure is elevated, so-called pulmonary venous hypertension (PVH). This pressure is transmitted back to the right side of the heart and the pulmonary arteries. The result is elevated pulmonary pressure throughout the pulmonary circulation. Some of this is a direct pressure transmission from the venous system backward and some can result from a reactive constriction of the pulmonary arteries.
Less commonly, pulmonary hypertension results from constriction, or stiffening, of the pulmonary arteries that supply blood to the lungs, so-called pulmonary arterial hypertension (PAH).
Whether it is pulmonary venous or pulmonary arterial hypertension, it becomes more difficult for the heart to pump blood forward through the lungs. This stress on the heart leads to enlargement of the right heart, and eventually fluid can build up in the liver and other tissues, such as in the legs.
What are normal pulmonary artery pressure ranges?
When the heart pumps blood, it is referred to as systole, and when the heart fills with blood it is referred to as diastole. Normal pulmonary artery pressures range from an upper pressure (systolic) of 15-30 mmHg and a lower pressure (diastolic) of 4-12 mmHg. These values can be obtained approximately by an ultrasound of the heart (echocardiogram), and more accurately using a catheter to measure the pressures in the pulmonary circulation (right heart catheterization).
What causes pulmonary hypertension?
There are many causes of pulmonary hypertension. Often more than one mechanism is involved in a specific disease process. This can also change as the disease progresses.
- Diseases that affect the flow out of the heart to the rest of the body result in backflow of blood (stacking of blood) that raises pulmonary venous pressures leading to pulmonary hypertension.
- Hypoxic pulmonary vasoconstriction is the process in which the lung vessels narrow in an attempt to divert blood from poorly functioning segments of the lung. For instance, when pneumonia develops, a portion of the lung becomes inflamed and works poorly in performing the functions of the lung (adding oxygen and removing carbon dioxide from the blood). This process diverts blood from these poorly working areas and sends it to better-functioning lung tissue. However, a problem develops when all the blood has a low oxygen level (hypoxia). This causes constriction of the vessels on the pulmonary arterial side and hence raises the pressure.
- Remodeling of blood vessels also occurs in some diseases whereby the inner lining (lumen) of the vessel becomes narrowed due to inappropriate growth of the tissue within and around the vessel. Masses and scarring from other diseases can compress and narrow vessels causing increased resistance to flow and resulting in elevation of pressures.
- In a fairly common parasitic infection in the Middle East (schistosomiasis), the blood vessels in the lung become blocked by the parasites causing pulmonary artery hypertension.
- Some substances cause constriction of the blood vessels. Pulmonary hypertension has been rarely reported with the use of anti-obesity drugs, such as dexfenfluramine (Redux) and Fen/Phen. These medications have seen been removed from the market. Some street drugs, such as cocaine and methamphetamines, can cause severe pulmonary hypertension.
- Some diseases raise pulmonary pressures to cause pulmonary artery hypertension for unclear reasons. Perhaps an unknown toxin or chemical affects the blood vessels by causing constriction or inappropriate growth of the tissue within or around the vessel. For example, there is a condition known as portopulmonary hypertension that is a result of liver failure. When these individuals receive a liver transplant, pulmonary hypertension disappears suggesting that the failing liver is unable to clear some biochemical that leads to pulmonary artery hypertension.
What causes idiopathic pulmonary hypertension?
Primary pulmonary hypertension has no identifiable underlying cause. This term is mainly a historical name and is no longer used. The current term used to describe this condition is idiopathic pulmonary hypertension. Idiopathic pulmonary hypertension is more common in young people and more common in females than males.
Idiopathic pulmonary hypertension unusually is an aggressive and often fatal form of pulmonary hypertension. Whereas it is known that arterial obstruction is caused by a building up of the smooth muscle cells that line the arteries, the underlying cause of the disease has long been a mystery.
A genetic cause of the familial form of idiopathic pulmonary hypertension, now referred to as Heritable PAH, has been discovered. It is caused by mutations in a gene called BMPR2. BMPR2 encodes a receptor (a transforming growth factor beta type II receptor) that sits on the surface of cells and binds molecules of the TGF-beta superfamily. Binding triggers conformational changes that are shunted down into the cell's interior where a series of biochemical reactions occur, ultimately affecting the cell's behavior. The mutations block this process. This discovery may provide a means of genetic diagnosis and a potential target for the therapy of people with familial (and possibly also sporadic) primary pulmonary hypertension.
Which diseases are common in people with the condition?
There are no clear statistical data on the prevalence of pulmonary hypertension. Since pulmonary hypertension is seen in multiple different conditions, it is perhaps better to look at the prevalence in each condition. It is fairly common in patients with heart failure, COPD, and sleep apnea. It occurs in 7% to 12% of patients with collagen vascular disease, and in less than 5% of HIV patients.
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What are the warning signs of pulmonary hypertension?
Many people with pulmonary hypertension may have no symptoms at all, especially if the disease is mild or in the early stages.
Pulmonary hypertension symptoms may include:
- Shortness of breath that worsens with activity
- Other common complaints are cough, fatigue, dizziness, and lethargy.
- With the advancement of the condition and ensuing right heart failure, shortness of breath may become worse and retention of fluid in the body may increase (due to failure of the heart to pump blood forward) resulting in swelling in the legs.
- People may also complain of chest pain and angina.
- Depending on the underlying associated disease, pulmonary artery hypertension can have other manifestations. For example, characteristic skin changes seen in scleroderma, or the signs of liver disease seen in portopulmonary hypertension.
Signs of pulmonary hypertension may include:
- Rapid breathing, hypoxia (low oxygen level in the blood), and swelling in the legs.
- In severe pulmonary hypertension, the health care professional may hear louder than normal components of heart sounds when he or she listens to the heart with a stethoscope (auscultation).
- The doctor may also feel elevation of the chest wall when the heart pumps and this may indicate enlargement of the right side of the heart suggestive of pulmonary hypertension (right ventricular heave).
Classification of primary and secondary pulmonary hypertension
The conventional classification, primary (idiopathic) and secondary pulmonary hypertension, which also is called pulmonary arterial hypertension, has been reclassified and is now based on the main underlying cause, characteristics, and treatments of pulmonary hypertension. These terms were updated in 2013. This system classifies the condition based on five classes.
Pulmonary arterial hypertension including idiopathic previously referred to as primary pulmonary arterial hypertension), inherited pulmonary arterial hypertension, drug-induced pulmonary arterial hypertension
Pulmonary arterial hypertension is associated with the following:
- Connective tissue diseases like systemic lupus erythematosus, or scleroderma
- Liver disease (elevated pressures in the liver, portal hypertension);
- Congenital heart disease
- Schistosomiasis (a parasite infection that can clog the pulmonary arteries)
- Pulmonary veno-occlusive disease (very rare)
- Persistent pulmonary hypertension of the newborn
Pulmonary hypertension due to left heart disease:
- An elevation of pulmonary arterial pressure because of increased pulmonary venous pressure backing up into the lungs
- Heart failure due to left ventricular systolic or diastolic dysfunction
- Valvular heart disease
- Some congenital/acquired heart diseases
Pulmonary hypertension due to lung diseases and/or hypoxia (low oxygen levels). This includes:
- Chronic obstructive lung disease (COPD)
- Interstitial lung diseases
- Sleep apnea
- Chronic exposure to high altitudes
- Congenital lung disease
Chronic thromboembolic pulmonary hypertension (chronic blood clots to the lungs that don't dissolve, also termed CTEPH).
Pulmonary hypertension with unclear multifactorial mechanisms, for example:
- Blood disorders (including hemolytic anemias)
- Systemic disorders (such as sarcoid)
- Metabolic disorders where cellular chemistry is abnormal (such as glycogen storage diseases)
- Tumors, fibrosis, and other problems obstructing blood flow through the lungs
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Which types of doctors treat pulmonary hypertension?
Generally, pulmonary physicians (pulmonologists) and cardiologists treat pulmonary hypertension. Depending on the cause, other physicians also may be involved, such as sleep medicine doctors, rheumatologists, and perhaps even infectious disease specialists. Today, more healthcare professionals in the community are becoming adept at managing pulmonary hypertension. However, it is reasonable to get a second opinion regarding management at a tertiary, university setting, because the field of management of pulmonary artery hypertension is evolving rapidly.
How is pulmonary hypertension diagnosed?
The first step in the diagnosis of pulmonary hypertension is to clinically suspect it. This may be done as part of an evaluation of another disease that can lead to pulmonary hypertension (such as scleroderma or chronic obstructive pulmonary disease), or based on the patient's signs and symptoms as described above.
Echocardiogram, Doppler, heart catheterization
- Many tests, such as an echocardiogram, may be performed that may give clues to the possibility of pulmonary hypertension. A Doppler study must be performed with the echocardiogram, which enables the doctor to approximate the pulmonary artery pressures. These values are calculated based on the sound quality of the wave approaching and leaving the echocardiogram machine sensor/probe. This is based on the principle that explains why the sound of an approaching and then passing train varies.
- But the gold standard (the best test available) is right heart catheterization. This test entails inserting a catheter through the groin into the femoral vein, a large vein in the lower body (or under the collar bone or in the upper arm or neck into a large vein in the upper body), and advancing it to the right side of the heart. The catheter is connected to a device that can monitor and measure blood pressure in the right side of the heart and pulmonary arteries.
- During right heart catheterization, oxygen levels are measured during various positions of the catheter in the pulmonary circulation. This can help determine if a congenital or acquired hole has formed in the heart contributing to the elevated pulmonary pressures. Certain medications or activities can be administered or performed during the procedure to help with the assessment. Nitric oxide can be inhaled and in certain forms of PAH, a dramatic improvement in pressures can occur, suggesting specific treatment options such as the use of calcium channel blocker medication. Some patients have an exaggerated pulmonary pressure response to exercise and this too can be measured by utilizing arm exercise during the procedure. Titration of medications for pulmonary hypertension, while the catheter is in place, can help monitor the response to treatment and assist in optimizing therapy. This can assist in providing individualized therapy for patients with this complex disease.
Pulmonary hypertension is defined as the mean pulmonary artery blood pressure greater than 25 millimeters of mercury (mmHg) measured by right heart catheterization. The pressures can be much higher than 25 mmHg in some people. Therefore, pulmonary hypertension can be labeled as mild, moderate, or severe based on the pressures. Mean arterial pressure is calculated by multiplying the diagnostic pressure two times, adding the systolic pressure to that number, and then dividing by three (systolic is the upper number and diastolic is the lower number in measuring blood pressure). Normally, pulmonary blood pressure is a much lower pressure system than systemic blood pressure (which is usually measured with a blood pressure cuff).
What tests may be used in diagnosing pulmonary hypertension?
Other tests available for diagnosing pulmonary hypertension include an electrocardiogram (ECG, EKG), chest X-ray, and echocardiogram. An ECG may show some abnormalities that may be suggestive of right heart failure. Chest X-ray may also show enlargement of the chambers of the right heart. An echocardiogram (ultrasound of the heart) shows ultrasound images of the heart and can detect evidence of right heart failure and, with the use of Doppler, (as described previously) can estimate pressures in the pulmonary artery. These tests, in the right clinical setting, are very useful in diagnosing and managing pulmonary hypertension.
Other tests may be useful in evaluating the conditions leading to secondary pulmonary hypertension. For example, a ventilation-perfusion scan (V/Q scan) can suggest blood clots in the pulmonary arteries, or sometimes a CT scan of the chest can be used. The chest CT scan can detect pulmonary arterial clots but also can show abnormalities of the lung tissue and surrounding structures that can contribute to pulmonary hypertension.
Pulmonary function testing can be useful in diagnosing chronic obstructive pulmonary disease (COPD), and other lung diseases, and monitoring disease progression. This test can be used to detect many aspects of lung function including airflow and evidence of obstruction, lung volumes, and the capacity of the lung to extract oxygen from the air.
Sleep studies can confirm the diagnosis of sleep apnea and its severity and management options such as CPAP therapy.
What is the treatment for pulmonary hypertension?
The treatment for pulmonary hypertension depends on the underlying cause.
- If left-sided heart failure is the primary problem, then adequate treatment of the left heart failure by a cardiologist is the mainstay of treatment.
- In cases where hypoxia (low oxygen levels) due to any chronic lung disease, such as COPD, is the cause, then providing oxygen and appropriately treating the underlying lung disease by a lung doctor (pulmonologist) is the first step in treatment.
- In some patients, the elevated pressure may be related to obstructive sleep apnea syndrome (OSAS) and can be reduced with the use of a CPAP (a device that delivers positive airway pressure during sleep).
- In conditions, such as scleroderma, which often can cause pulmonary hypertension, a rheumatologist is involved in the treatment program.
- Anticoagulation (thinning the blood) may be a treatment option if the main underlying cause is thought to be a recurrent blood clot (chronic thromboembolic pulmonary hypertension). As indicated in a previous section, referral to a specialty center may be warranted for possible surgical removal of a blood clot (thromboendarterectomy).
- For patients with primary pulmonary hypertension (those with no underlying cause), more advanced therapy may be attempted. These drugs have complex mechanisms, but in general, they work by dilating (opening up) the pulmonary arteries and, therefore, by reducing the pressure in these blood vessels, and some help prevent the excessive overgrowth of tissue in the blood vessels (that decrease remodeling of the vessels, as described previously). Besides constriction, PAH can result in an actual structural change of the pulmonary arteries; whether it is due to chronically elevated pressures, the disease itself, or a combination of the two is not completely clear. These drugs also can delay and, in some cases, reduce the degree of remodeling of the pulmonary arteries.
What are pulmonary hypertension medications?
There are three major classes of drugs used to treat idiopathic pulmonary hypertension and pulmonary hypertension associated with collagen vascular diseases: 1) prostaglandins; 2) phosphodiesterase type 5 inhibitors; and 3) endothelium-receptor antagonists.
- Prostaglandins such as epoprostenol (Flolan), treprostinil (Remodulin, Tyvaso), iloprost (Ventavis). These drugs are very short-acting and often must be given intravenously or inhaled on a very frequent or continuous basis.
- Phosphodiesterase type 5 inhibitors such as sildenafil (Revatio, Viagra) and tadalafil (Adcirca, Cialis) are somewhat less effective than prostaglandins but are easily administered one to three times per day by mouth. (The dosing is much different when these drugs are used for erectile dysfunction.)
- Endothelium antagonists are the newest medications used for this condition. These include bosentan (Tracleer) and ambrisentan (Letairis). These medications are also given by mouth one to two times per day.
What other drugs treat pulmonary hypertension?
- A unique drug, riociguat (Adempas), is indicated for pulmonary hypertension due to chronic thromboembolic disease (CTEPH). The mechanism of action is different than the drugs above. It works by increasing the effect of nitric oxide causing increased pulmonary vasodilation.
- In rare cases, calcium channel blockers (CCBS) may be of benefit.
Currently, research is investigating the best ways to combine these medications for optimal clinical outcomes. It should be noted that these medications are extremely expensive. The companies that manufacture these medications often have programs to assist in funding. These more advanced therapies have also been used for other forms of pulmonary hypertension; however, no clinical studies have yet confirmed benefits in these situations.
Is there a cure for pulmonary hypertension?
Despite advances in various treatments, there is no cure for pulmonary hypertension.
What is the life expectancy for people with pulmonary hypertension?
Generally, the prognosis of pulmonary hypertension varies depending on the underlying condition that is causing it. For idiopathic or familial pulmonary hypertension, the overall prognosis depends on the severity and whether treatment was instituted. The statistics show survival of about 3 years in idiopathic pulmonary hypertension without any therapy. Some of the other factors may indicate an even poorer prognosis, which includes severe symptoms, age of onset greater than 45 years, evidence of right-sided heart failure, and failure to respond to treatment.
For patients with idiopathic pulmonary hypertension who get started on treatment and respond to it, the prognosis is better. Studies are underway to determine optimal treatment regimens.
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Kiely, D.G., et al. "Pulmonary hypertension: diagnosis and management." BBMJ. 2013;346:f2028
NIH. National Heart, Lung, and Blood Institute. "Pulmonary Hypertension."
Poms, A. and Kingman, M. "Inhaled treprostinil for the treatment of pulmonary arterial hypertension." Critical Care Nurse. April 2012;32(2)11.
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