Pulmonary hypertension

Causes of pulmonary hypertension

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

The walls of your pulmonary arteries can become stiff and thickened, or may be blocked by something such as a blood clot. This makes it harder for your heart to push blood through these arteries, which increases the pressure inside the vessels and results in pulmonary hypertension.

There can be many different reasons for the changes to your arteries. The World Health Organization (WHO) has classified pulmonary hypertension into five different 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 with the smaller branches of the pulmonary arteries. In PAH, these changes are usually the core medical problem, rather than a condition that has started somewhere else and then affected the pulmonary arteries.

Unlike the other types of pulmonary hypertension, PAH can therefore be treated directly, while in other cases 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 can 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 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 – when capillaries (tiny blood vessels) grow within the lungs, causing 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 (main artery from the left side of the heart) to the pulmonary artery – this is often done to treat congenital heart disease and increase the blood supply to the lungs
• portal hypertension – a condition where the blood pressure inside the liver is abnormally high, leading to the development of swollen veins
• HIV – one in 200 people with HIV will develop PAH
• certain medications or drugs – such as fenfluramine, which is now 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 – when you have had your spleen surgically removed
• sickle cell anaemia (see below)

Sickle-cell anaemia is an inherited disorder where your red blood cells are abnormal and die prematurely, leading to a shortage of red blood cells. The lack of red blood cells means that haemoglobin, a protein normally found in these cells, is released into the blood.

The haemoglobin seeks out and destroys nitric oxide. This is a substance produced by your body and used to widen blood vessels. Without nitric oxide, your blood vessels remain narrow, which increases the blood pressure within them and can cause pulmonary hypertension.

Persistent pulmonary hypertension of the newborn

This is a type of pulmonary hypertension 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 the 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 baby 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 atria (upper chamber)
• the left ventricle (lower chamber)
• the aortic and mitral valves – one-way valves that allow blood to flow through the heart in the correct direction

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

For example, the mitral valve, which is located between the left atria and left ventricle, can become narrowed. If this happens, there will be a build-up of blood trying to get through the valve, which will increase blood pressure in the left atria. This could in turn increase pressure in the blood vessels between the lungs and the heart, and then 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 collection 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 difficult 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 types of conditions can restrict the amount of oxygen that is getting into the lungs, and therefore into the blood. A low level of oxygen in the blood causes the pulmonary arteries to constrict (become narrower). Because these vessels are narrower, the blood is squeezed into a smaller space, increasing the blood pressure and resulting 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 have 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.

Treating pulmonary hypertension

If your pulmonary hypertension is caused by an underlying condition, your treatment will focus on tackling it. 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. There is one centre in Scotland at the Golden Jubilee National Hospital in Clydebank.

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

Background therapy

Background therapy includes:

• anticoagulant medicines
• diuretics
• oxygen
• digoxin

These are explained in more detail below.

Anticoagulant medicines

PAH can increase your risk of venous thromboembolism, which is when a blood clot forms in a vein and then breaks free. The clot can become trapped in a blood vessel, blocking the vessel and the blood supply. If this blocks one of the blood vessels supplying your lungs, this is called a pulmonary embolism.

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

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

Diuretics

Diuretic medicines are used to remove excess fluid from the body by increasing the production and flow of urine. Diuretics may be used in pulmonary hypertension to treat any fluid retention and swelling (oedema). This can occur if pulmonary hypertension starts to cause heart failure (when your heart struggles to pump blood around your body).

Possible 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

Diuretics can also disrupt your levels of electrolytes (minerals in your blood, such as potassium) and affect your kidney function. Because of this, your kidneys and blood will be monitored while you are taking diuretics.

Oxygen

If you have low oxygen levels in your blood, you may need to be treated with oxygen. This involves inhaling air that has a higher amount of oxygen in it than normal. This increases the amount of oxygen in your blood and should improve your symptoms.

Digoxin

If your pulmonary hypertension leads to heart failure, you may be treated with digoxin. This increases the strength of your heart muscle contractions and can slow down your heart rate.

Calcium channel blockers

Calcium channel blockers are medicines normally used to treat high blood pressure (hypertension). They work by relaxing the muscles that make up the walls of your arteries. This widens your arteries and reduces your blood pressure.

Possible calcium channel blockers include:

• nifedipine
• diltiazem

Calcium channel blockers 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 if calcium channel blockers will be suitable for you. This involves taking some of the medication and then checking the blood pressure in your pulmonary arteries 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 if they are no longer effective, further treatments can be tried. These are called targeted therapies and include the following medicines:

• bosentan
• sildenafil
• iloprost
• epoprostenol

These are explained in more detail below.

Bosentan

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

You may spend a day in hospital starting treatment and should then be able to return home and carry on taking the medicine. If after 8-16 weeks your condition has not improved (or has got worse), you may be given additional treatment as well as or instead of bosentan.

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

Bosentan will not be suitable for you if you:

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

Women who could get pregnant must use contraception if they are taking bosentan. Bosentan can interact with hormonal contraception, such as the combined contraceptive pill, so it is better to use an alternative 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 starting treatment and should then be able to return home and carry on taking the medicine. How long you can take sildenafil for will depend on your condition. If at any time your condition gets worse, you may be given additional treatment as well as or instead of sildenafil.

Sildenafil may not be suitable for you 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 problem with your liver
• have recently had a heart attack or stroke
• have severe low blood pressure
• have certain eye conditions

Iloprost

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

You will need to stay in hospital for up to three days to be trained in using the nebuliser and to monitor your response. After this time, you should be able to return home and keep taking the medicine yourself.

How long you need to take iloprost for will depend on your condition. You may need to continue taking 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. Epoprostenol needs to be given through an intravenous infusion, which means a constant drip of medicine goes through a narrow tube into a vein in your arm.

Treatment with epoprostenol will begin in hospital. It may take one or two weeks to find the correct dose for you. After this time, it is possible, with special training and equipment, for you or your carer to learn how to take this medicine yourself at home.

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

Epoprostenol may not be suitable for you 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. This involves transplanting the healthy heart and lungs from a donor into you. However, because of a shortage of donors, these are rarely carried out. There are probably fewer than 10 heart-lung transplants a year in the UK.

Read more on heart-lung transplants.

Don’t include personal information e.g. name, location or any personal health conditions.

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.