Pulmonary hypertension

Pulmonary hypertension is caused by changes to the pulmonary arteries, the blood vessels that carry blood from your heart to your lungs.

The walls of these arteries can become stiff and thickened, or they can be blocked by something such as a blood clot. This makes it harder for your heart to push blood through them. The pressure inside the vessels goes up, and that is what leads to pulmonary hypertension.

There can be many different reasons for these changes to your arteries. The World Health Organization (WHO) has grouped pulmonary hypertension into five types, depending on the underlying cause:

• pulmonary arterial hypertension (PAH)
• pulmonary hypertension associated with left heart disease
• pulmonary hypertension associated with lung disease and hypoxia
• pulmonary hypertension due to blood clots
• pulmonary hypertension due to other causes

Pulmonary arterial hypertension (PAH)

Pulmonary arterial hypertension (PAH) is caused by problems in the smaller branches of the pulmonary arteries. In PAH, these changes are usually the core medical problem, rather than a condition that started somewhere else and then affected the pulmonary arteries.

Unlike the other types of pulmonary hypertension, PAH can be treated directly. In the other types, the underlying cause is treated first.

PAH is further divided into specific subtypes, outlined below.

Idiopathic PAH

Idiopathic means the cause is unknown. If tests cannot find an underlying reason for your PAH, you may be diagnosed with idiopathic PAH. This is rare, affecting one or two people in every million each year.

Familial PAH

Some cases of PAH run in families. It is thought that a particular genetic mutation (a change in one of the genes you inherit from your parents) can cause PAH. In up to 10% of PAH cases, there may be a family history of the condition.

PAH associated with other conditions

PAH can be associated with conditions that affect your blood vessels, such as:

• pulmonary veno-occlusive disease, a rare condition that causes high blood pressure in the lungs
• pulmonary capillary hemangiomatosis, where capillaries (tiny blood vessels) grow within the lungs and cause blockages

Other conditions or treatments associated with PAH include:

• a condition affecting the structure or composition of your body tissue, such as scleroderma (a condition that causes hardening of the skin)
• surgery to artificially connect the aorta (the main artery from the left side of the heart) to the pulmonary artery. This is often done to treat congenital heart disease and to increase the blood supply to the lungs.
• portal hypertension, a condition where the blood pressure inside the liver is abnormally high, leading to swollen veins
• HIV. One in 200 people with HIV will develop PAH.
• certain medicines or drugs, such as fenfluramine, which is no longer available, and amphetamines, a type of illegal drug
• disorders of the thyroid gland
• glycogen storage disorder (glycogen is a carbohydrate that produces short-term energy)
• splenectomy, which means your spleen has been surgically removed
• sickle cell anaemia (see below)

Sickle cell anaemia is an inherited disorder in which your red blood cells are abnormal and die early, leading to a shortage of red blood cells. Because there are so few red blood cells, haemoglobin, a protein normally found inside them, is released into the blood.

The haemoglobin seeks out and destroys nitric oxide, a substance your body produces to widen blood vessels. Without nitric oxide, your blood vessels stay narrow. That raises the blood pressure within them and can cause pulmonary hypertension.

Persistent pulmonary hypertension of the newborn

This type of pulmonary hypertension is estimated to affect two in every 1,000 newborn babies.

It has been linked to the mother taking non-steroidal anti-inflammatory drugs (NSAIDs) during the third trimester of pregnancy (week 27 to the birth).

Conditions that may also be associated with persistent pulmonary hypertension of the newborn include:

• severe pulmonary hypoplasia, when your baby's lungs are seriously underdeveloped
• hypoglycaemia, an abnormally low level of glucose in the baby's blood
• sepsis, a life-threatening illness caused by the baby's body overreacting to an infection
• meconium aspiration syndrome, when a newborn breathes in a mixture of amniotic fluid (which surrounds them in the womb) and meconium (their first faeces), which can block their airways

Left heart disease

Pulmonary hypertension may sometimes be associated with diseases affecting the left side of your heart, which pumps blood around the body. The left side of the heart is made up of:

• the left atrium (upper chamber)
• the left ventricle (lower chamber)
• the aortic and mitral valves, one-way valves that keep blood flowing through the heart in the correct direction

Blood goes from the pulmonary arteries to the lungs and then to the left side of the heart. So any problem with the left side of the heart could have a backward effect on this circuit and affect the pulmonary arteries. This in turn could cause pulmonary hypertension.

For example, the mitral valve sits between the left atrium and left ventricle. If it becomes narrowed, blood builds up trying to get through it, and blood pressure in the left atrium rises. That can raise pressure in the blood vessels between the lungs and the heart, feed back, and increase pressure in the pulmonary arteries, leading to pulmonary hypertension.

Up to 60% of people with a condition causing severe left ventricle dysfunction have pulmonary hypertension. Almost all people with a severe mitral valve condition, and nearly two-thirds of those with a severe aortic valve condition, have pulmonary hypertension.

Lung disease and hypoxia

Pulmonary hypertension can also be associated with lung diseases or hypoxia (a shortage of oxygen in the body). This includes:

• chronic obstructive pulmonary disease (COPD), a group of lung diseases, such as emphysema, where people have trouble breathing. Over half of people with advanced COPD may have pulmonary hypertension, although it is usually mild.
• interstitial lung disease, a group of lung disorders that cause scarring of your lung tissue, making it hard to get enough oxygen into your body. Around a third of people with interstitial lung disease may have pulmonary hypertension.
• sleep-disordered breathing, conditions that affect your breathing while you are in deep sleep, such as obstructive sleep apnoea

These conditions can restrict the amount of oxygen getting into the lungs, and so into the blood. A low level of oxygen in the blood causes the pulmonary arteries to constrict (become narrower). With the vessels narrower, the blood is squeezed into a smaller space. That increases blood pressure and results in pulmonary hypertension.

Blood clots

A foreign object, usually a blood clot, blocking or obstructing a vein may sometimes cause pulmonary hypertension.

When a blood clot blocks one of the blood vessels supplying your lungs, this is called a pulmonary embolism. After a pulmonary embolism, up to two in 100 people may develop pulmonary hypertension.

Other causes

Other, less common, causes of pulmonary hypertension include:

• sarcoidosis, a condition that causes inflammation (swelling) of different organs, including the lungs and lymph nodes
• histiocytosis X, a condition that causes swelling in the blood vessels in the lungs
• compression of the blood vessels in the lungs, for example by a tumour

Diagnosing pulmonary hypertension is not always straightforward, because its symptoms look so much like those of other heart and lung problems. Because of this, it can take up to three years for someone to get the correct diagnosis.

Even so, since pulmonary hypertension can become serious, you should see your doctor as soon as you notice any symptoms. Your doctor will usually ask you about:

• your symptoms and how they are affecting your daily life
• your family history, since some forms of pulmonary hypertension can run in families
• any medication you are currently taking
• any other health conditions you have

Tests

A number of tests can help diagnose pulmonary hypertension or find an underlying condition behind it. Your doctor may arrange these directly, or you may be sent to a hospital to have them done.

Echocardiogram

An echocardiogram is a type of ultrasound scan used to check how well your heart is working. Ultrasound uses high-frequency sound waves to build a picture of the inside of your body, such as your heart, and it can be used to estimate the pressure inside your pulmonary arteries.

Electrocardiogram

An electrocardiogram, or ECG, records the rhythm and electrical activity of your heart. Small sticky pads called electrodes are placed on your arms, legs and chest and connected by wires to an ECG machine.

Each time your heart beats, it gives off a tiny electrical signal, and the ECG machine traces these signals onto paper.

Chest X-ray

An X-ray uses high-energy radiation to reveal problems in your bones and certain body tissues.

A chest X-ray can help rule out other causes of your symptoms. For example, scarring in the lungs can also lead to shortness of breath. It can also show whether your heart is larger than normal, since pulmonary hypertension makes the right side of your heart work harder, which can cause it to enlarge.

Lung function tests

Lung function tests, sometimes called breathing tests, check how well your lungs are working. They measure how quickly you can move air in and out of your lungs, how much air your lungs can hold, and how well they move oxygen into your blood while removing carbon dioxide.

For these tests, you breathe in and out through a lung function machine, and the results help identify different lung conditions.

Exercise tests

Exercise tests check your symptoms while you carry out some form of physical activity. For instance, you might be asked to walk for six minutes, either on a treadmill or up and down a corridor, while your heart rate and blood pressure are monitored. This can help identify underlying causes of your symptoms.

Ventilation and perfusion scan

This scan measures the airflow and blood flow in your lungs. It can help detect blood clots in your blood vessels that might be causing pulmonary hypertension.

Blood tests

A blood sample may be taken and tested to rule out other conditions.

Confirming the diagnosis

These tests can point strongly toward pulmonary hypertension, but the diagnosis is only confirmed by directly measuring the blood pressure in:

• the right ventricle, the lower chamber of your heart that pumps blood to your lungs
• your pulmonary arteries, which carry blood from the right side of your heart to your lungs

This blood pressure is measured through a procedure called right heart catheterisation.

Right heart catheterisation

In this procedure, a thin, flexible tube called a catheter is inserted into a vein in your neck, arm or groin. The catheter is then guided into the right side of your heart and into your pulmonary arteries. Along with measuring blood pressure, it can also measure:

• how much blood the right side of your heart is pumping to your lungs
• the resistance your heart has to work against to push blood to your lungs, known as pulmonary vascular resistance
• the amount of oxygen in the blood returning to your heart

If the pressure in your pulmonary arteries is higher than a certain level, you will be diagnosed with pulmonary hypertension.

If these tests uncover an underlying cause, you will be diagnosed with a specific type of pulmonary hypertension. If no cause can be found, the diagnosis will be idiopathic pulmonary arterial hypertension.

If your pulmonary hypertension is caused by an underlying condition, treatment will focus on that condition first. If the cause is treated early, it may be possible to prevent permanent damage to your pulmonary arteries (the blood vessels supplying your lungs).

If you have pulmonary arterial hypertension (PAH), you will be referred for treatment at a centre that specialises in PAH.

Several different medicines can be used to treat PAH and the other types of pulmonary hypertension. You will usually be started on conventional therapy, also called background therapy, and then your treatment will be changed or increased as needed. Further treatment is called targeted therapy.

Background therapy

Background therapy includes:

• anticoagulant medicines
• diuretics
• oxygen
• digoxin

Each is explained below.

Anticoagulant medicines

PAH can raise your risk of venous thromboembolism. This is when a blood clot forms in a vein and then breaks free. The clot can get trapped in a blood vessel and block it, cutting off the blood supply. If the blocked vessel is one of those supplying your lungs, it is called a pulmonary embolism.

Anticoagulant medicines reduce the ability of the blood to clot. Taking an anticoagulant such as warfarin may therefore lower your risk of venous thromboembolism.

These medicines can cause side effects, such as increased bleeding, so you will be monitored carefully while you take them.

Diuretics

Diuretics remove extra fluid from the body by increasing the production and flow of urine. In pulmonary hypertension they may be used to treat fluid retention and swelling (oedema). This can happen if the condition starts to cause heart failure (when your heart struggles to pump blood around your body).

Diuretics that may be used include:

• furosemide
• amiloride
• spironolactone

Diuretics can cause some side effects, such as:

• mild tummy upset
• postural hypotension, when your blood pressure drops suddenly after movement (for example, feeling dizzy after standing up)
• a dry mouth
• rashes
• headaches
• confusion

They can also upset your levels of electrolytes (minerals in your blood, such as potassium) and affect how well your kidneys work. Because of this, your kidneys and blood will be checked while you are on diuretics.

Oxygen

If the oxygen level in your blood is low, you may need oxygen treatment. You breathe in air that contains more oxygen than normal. This raises the amount of oxygen in your blood and should ease your symptoms.

Digoxin

If your pulmonary hypertension leads to heart failure, you may be given digoxin. It makes your heart muscle contract more strongly and can slow your heart rate.

Calcium channel blockers

Calcium channel blockers are medicines normally used for high blood pressure (hypertension). They relax the muscles in the walls of your arteries, which widens the arteries and lowers your blood pressure.

Calcium channel blockers that may be used include:

• nifedipine
• diltiazem

They may work for people with idiopathic PAH (PAH with no known cause), but the effect in other types of PAH is less clear.

You will need a vasoreactivity test to find out whether these medicines suit you. You take some of the medicine, and then the blood pressure in your pulmonary arteries is checked to see if it has fallen. If it has, you may be prescribed calcium channel blockers.

Targeted therapy

If calcium channel blockers were not suitable for you, or they are no longer working, other treatments can be tried. These are called targeted therapies and include the following medicines:

• bosentan
• sildenafil
• iloprost
• epoprostenol

Each is explained below.

Bosentan

Bosentan tablets may be taken to improve your symptoms and your ability to exercise. You usually take two tablets twice a day (morning and evening), though the dose can vary.

You may spend a day in hospital when you start, and then you should be able to go home and carry on taking the medicine. If your condition hasn't improved after 8 to 16 weeks (or has got worse), you may be given extra treatment as well as, or instead of, bosentan.

Bosentan can raise the levels of some enzymes in the liver, and this can lead to liver damage. Enzymes are proteins that speed up and control chemical reactions in the body, such as digestion. So your liver will need to be checked once a month for as long as you take bosentan.

Bosentan will not be suitable if you:

• already have a liver problem
• are taking ciclosporin (a medicine that suppresses your immune system)
• are pregnant

Women who could become pregnant must use contraception while taking bosentan. Bosentan can interact with hormonal contraception, such as the combined contraceptive pill, so it is better to use another method, such as condoms.

Sildenafil

Sildenafil tablets are usually taken three times a day to improve your ability to exercise.

You may spend a day in hospital when you start, and then you should be able to go home and carry on taking the medicine. How long you can take sildenafil depends on your condition. If your condition gets worse at any point, you may be given extra treatment as well as, or instead of, sildenafil.

Sildenafil may not be suitable if you:

• are also taking medicines or drugs that contain nitrates (organic nitrates are often used to treat angina, and amyl nitrate is a recreational drug commonly known as 'poppers')
• have a severe liver problem
• have recently had a heart attack or stroke
• have severe low blood pressure
• have certain eye conditions

Iloprost

Iloprost is inhaled through a nebuliser, a device that turns the liquid medicine into a mist you breathe into your lungs. You may need to take it around six to nine times a day, and each dose can take up to 10 minutes to inhale.

You will need to stay in hospital for up to three days so you can be trained to use the nebuliser and your response can be watched. After that you should be able to go home and keep taking the medicine yourself.

How long you need iloprost depends on your condition. You may need to continue with it, possibly alongside other treatments, until your condition worsens and you need epoprostenol (see below).

Iloprost may not be suitable if:

• you have a peptic ulcer
• you have recently had a heart attack or stroke
• your pulmonary hypertension is caused by pulmonary veno-occlusive disease (a rare condition that causes high blood pressure in the lungs)
• your pulmonary hypertension is unstable, with advanced right heart failure

Epoprostenol

Epoprostenol (its full name is epoprostenol sodium) may be used if you do not respond to other treatments. It has to be given by intravenous infusion, which means a constant drip of medicine runs through a narrow tube into a vein in your arm.

Treatment with epoprostenol begins in hospital. It may take one or two weeks to find the right dose for you. After that, with special training and equipment, you or your carer can learn to give the medicine at home.

Once you start epoprostenol, you may not be able to stop. Coming off it can make your pulmonary hypertension return rapidly, so you may need to take it for the rest of your life. That is why epoprostenol is considered last, after other treatments have not worked or your condition has got worse.

Epoprostenol may not be suitable if you have heart failure caused by a problem with the left side of your heart, or if you have or develop pulmonary oedema (fluid on the lungs).

Heart-lung transplant

For severe pulmonary hypertension, a heart-lung transplant may be a treatment option. The healthy heart and lungs of a donor are transplanted into you. But because there is a shortage of donors, these operations are rarely carried out.

Pulmonary hypertension is a serious illness, and it usually keeps getting worse over time. Because the symptoms can be quite general, diagnosis is sometimes delayed.

A symptom like breathlessness can affect your quality of life a great deal, since it may stop you from carrying on with your everyday activities. This is why it's important to start treatment as early as possible, so your symptoms can improve.

If an underlying condition is causing your pulmonary hypertension, that condition needs to be treated first. Doing so can, in some cases, prevent lasting damage to your pulmonary arteries.

Back in the 1980s, people diagnosed with PAH lived for less than three years, on average. Thanks to newer medicines, people today may be able to survive for much longer. How the illness progresses will depend on how early it's diagnosed, how advanced your symptoms are, and whether you have an underlying health condition.