Treatment for Pulmonary Hypertension related to scleroderma in 2006
Clive Handler, Consultant in Pulmonary Hypertension, Clare Das, Senior Specialist Nurse, Professor Christopher Denton, Consultant Rheumatologist, Geraldine Brough, Specialist in Rheumatology, Gerry Coghlan, Consultant Cardiologist
The National Pulmonary Hypertension Unit and Centre for Rheumatology, Royal Free Hospital,London, NW3 2QG, UK
As well as causing scarring or fibrosis of the skin, scleroderma (systemic sclerosis) can lead to similar changes in the blood vessels and other internal organs. A small proportion (8%) of patients, more commonly those with limited compared to diffuse SSc, develop another serious condition called pulmonary arterial hypertension (PAH) - a high pressure in the lung arteries. “Ordinary” hypertension - is a high pressure in the arteries that carry fresh blood around the body. Whereas ordinary hypertension is common, can be effectively treated with several different types of tablets and most patients don't know they've got it, PAH is much rarer, affecting around 40 people in every million. Patients get breathless and tired and it is more serious.
Until recently, we had little to offer patients with PAH. Now we have several different drugs and new ones are coming along. Although none of these “cure” PAH, they can, in some patients, improve symptoms, reduce the pressure in the lungs, and help patients live a longer and more active life by stabilising the condition. This short article will tell you about PAH and how we treat it. Scleroderma patients, their families, and their doctors and nurses, are justified in feeling much happier and more optimistic about the future.
What is PAH? In people with PAH the walls of the pulmonary (lung) arteries, which are the blood vessels carrying “stale” blood from the right side of the heart to the lungs, get thick and narrowed. This makes it more difficult for blood to get through the lungs and puts an increasing amount of pressure on the right heart pumping chamber (right ventricle), which gets weak (heart failure). Patients feel progressively breathless and unable to walk more than short distances. Patients with scleroderma often do not get swollen ankles because of their tight skin. When the heart gets very weak, patients may lose their appetite and lose weight. Patients with PAH are also more vulnerable to getting blood clots in the lungs because the flow of blood in their lung arteries is slow.
Are there other reasons why the pressure may be high in the lung arteries?
There are several other much more common causes of breathlessness (bronchitis, asthma, heart disease, and being unfit) than PAH. These have to be excluded before PAH is diagnosed.
Any problem with the left heart pump (the left ventricle) – for example, a weakness of the muscle due to a heart attack or high blood pressure - can cause a high pressure in the lungs. People who get blood clots in their lung arteries, and individuals who have holes in their heart, may also get high pressure in the lung arteries.
How serious is PAH? It depends on how high the pressure is. Whereas some patients with only a slightly high pressure in the lungs can lead a very active and productive life, as long as they don't over-do things, others with severe PAH get more and more breathless quite quickly. Without treatment the outlook is poor in more severe cases – such that in very severely affected patients their future is similar to some forms of aggressive cancer.
How is PAH diagnosed? In common with other internal complications of scleroderma it is important to diagnose PAH as early as possible. Therefore all scleroderma patients should have regular screening tests.
In order to pick up those patients who may be developing PAH, we recommend that they also have
We analyse all these bits of information to help us decide whether further tests are necessary.
What is the most accurate test to diagnose PAH and how is it done? A right heart catheter is the most important test. It allows measurement of the pressure in the lung arteries. PAH cannot be reliably diagnosed without this test. Patients take all their drugs on the day of the procedure (except warfarin which should be stopped three days before, and diabetic tablets on day of the procedure). Patients lie on an X ray table and a thin tube is inserted under local anaesthetic, into the vein in the groin (femoral vein) and then positioned, using X ray guidance, into the right side of the heart and then into the lung arteries. Most patients do not feel anything more than a pushing sensation. A pressure of 25 mm Hg or more at rest or 30 mm Hg or more during arm exercise means that the patient has PAH. The catheter tube is also used to take blood samples and to measure the amount of blood pumped around the body, and the resistance to the flow of blood in the lungs. This is called the cardiac output and will be low in patients with a weak heart.
How does the result affect treatment? Only patients with PAH respond to the available drugs, patients with high pressure in the lung arteries for other reasons (such as left heart failure) need different treatments.
What if the tests are normal? If we think that a patient has not got PAH, we would see the patient in a year. If the tests are borderline, we would repeat the tests in six months.
If we are certain that a patient does not have PAH, we refer them back to their usual physician for continued monitoring.
What treatments are given to patients with PAH? We divide the types of treatment into two categories – basic and advanced.
These do not affect the disease process but relieve symptoms of PAH and heart failure.
Oxygen We encourage patients who are very breathless to use oxygen for most of the day, provided the oxygen level in the blood is low. This can be done with a condenser obtained via the GP or arranged by their PAH centre. Small portable oxygen machines are also available and allow patients to leave home.
Warfarin This anticoagulant thins the blood and reduces the likelihood of blood clots in the lungs. It might also reduce the thickening in the wall of the lung arteries. The GP or local hospital monitor the blood International Ratio (INR) every two months, and advise patients of the correct dose to keep the INR between 2-3. Warfarin may have to be stopped if patients get recurrent nose bleeds or bleeding from the stomach.
Water tablets (diuretics) This reduces fluid retention in the legs and lungs and makes it easier for patients to breathe. Spironolactone and, in addition, when necessary, furosemide and bumetanide, are used. The dose of these diuretics may need to be increased if patients develop a lot of water retention. The dose is decreased if the kidney function deteriorates.
Digoxin (Foxglove) This is used to help strengthen the heart beat.
These treatments reduce thickening in the lung arteries. There are three different type of drugs. They have all been shown to improve the six minute walking distance and lower the pressure in the lungs.
Endothelin antagonists
Bosentan is usually the first to be used and we have most experience with this. It is given as a tablet twice a day. Blood tests are done monthly because a small proportion of patients get liver damage which disappears when the drug is stopped. It slows down the rate of progression of the thickening in the lung arteries and this improves breathing by reducing the resistance to blood flow through the lung arteries. It may lower the blood pressure and some patients feel light headed if they stand up quickly. We have shown that Bosentan has improved survival in patients with SSc-PAH compared to previous treatment approaches.
Sitaxentan is a relatively new drug but we do not yet know how it compares to Bosentan, although in clinical trials it appears to be similarly effective for PAH.
Sildenafil
Also known as Viagra®, sildenafil appears to be a useful drug in PAH. It is often added on to bosentan in patients who do not respond adequately to bosentan alone. We call this combination therapy. We sometimes use sildenafil instead of bosentan as first line treatment, for example in patients who would not tolerate bosentan because of liver problems, or other medications. Patients are given sildenafil 20 mg twice a day and then, this dose is increased to 50 mg twice a day. Side effects include headache and lowering of the blood pressure.
Drugs similar to sildenafil are being tested and we look forward to the results of these trials.
Prostanoids
These were the first drugs used as advanced therapy. The drug, prostacyclin, can be given by three routes: inhalation, into the skin (subcutaneous), usually in the abdomen, and most effectively, through a vein directly into the bloodstream. Inhalations should be given six times per day but this is time consuming. The subcutaneous form is painful and the indwelling needle has to be moved to different sites on the skin. The intravenous form uses a tube placed in a large vein under the collarbone. This procedure carries a small risk of a punctured lung and infection and patients need to be taught how to look after the tube to avoid infection. The doses of prostanoids are increased periodically. These drugs are very effective in helping patients feel better and being more active.
What treatments are offered when the condition deteriorates despite medication? Lung transplantation is considered for patients with severe PAH. It has become much more difficult to get donor lungs. The operation, which carries a significant risk is done at only a few hospitals in the UK.
We occasionally offer a treatment called atrial septostomy. This creates a hole between the collecting chambers but only a very small number of patients are suitable for this treatment.
Living with PAH Although a serious condition, a lot can be done by the team looking after you to provide support for you and your family, and practical advice to help you cope with the condition. You will be told to do as much as you can do comfortably, to enjoy the good days and do not overdo things when you are not in the mood. You will be advised what to do about work. It is useful to have a few good friends to talk to. Patient organisations provide wonderful support and advice on all aspects of your condition, including travelling abroad. They provide the opportunity for you to meet other people with SSc and PAH and many patients find this very helpful and comforting.
It is very important to take the medication prescribed in the correct dose and at the right time of day. Your PAH centre will have a telephone advice line . Keep in touch with your PAH centre and let them know how you are, particularly if you feel you are getting worse. Clinic appointments are important and essential for the medical team to be able to see you and examine you. Blood tests and other investigations may be necessary to follow your condition.
You may be asked to participate in a drug trial but this would usually involve extra visits to hospital for assessments. Many patients enjoy being part of trials because they are reviewed frequently and given prompt care. The choice to enter a trial or not, is completely up to the patient.
Conclusion
As with all medical conditions, effective treatments and cures rely on a detailed understanding of the cause of the problem. We are making considerable progress and are working very hard to improve the health and well being of our scleroderma patients in several ways. The last five years has seen major advances in the outcome for patients with SSc-PAH and we anticipate further advances in the near future.