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Welcome to the

PHA SA South Africa Website

This website is for anyone who suffers from Pulmonary Hypertension (PH) as well as their friends and family.

Here you will find information about the condition, as well about the PHA South Africa organisation.

Figure of

Pulmonary Hypertension

What is

Pulmonary Hypertension

Pulmonary Hypertension, or PH, is a disease affecting the arteries of the lungs. It can strike anyone regardless of age, gender, social or ethnic background. People affected with this disease suffer from continuous high blood pressure in the lungs which results in an enlargement of the heart, and can lead to heart failure

The heart and circulatory system2

To understand what PH is, it first helps to understand a bit about the circulatory system. As shown in the figure, the heart pumps oxygen-poor blood to the lungs so the blood can take up oxygen. Blood that is oxygen-poor is normally shown on diagrams as blue, whereas oxygen-rich blood returning from the lungs is normally shown in red.

During periods of exercise, the heart beats more quickly to get more oxygen to the muscles. At the same time, the blood vessels carrying blood to the lungs (the pulmonary arteries) expand to allow more blood through. The pulmonary arteries do this by stretching slightly. In a person with PH, the walls of the pulmonary arteries are thicker, so are less able to stretch.

Read More about World PH Day May 5th.

Healthy

Pulmonary Artery

Artery stretches in response to increased heart rate

PH patient

Pulmonary Artery

Thickened artery cannot stretch enough in response to increased heart rate

Symptoms of

Pulmonary Hypertension

  • Breathlessness or shortness of breath, especially with activity
  • Chest pain(also called angina pectoris), especially during physical activity
  • Dizziness/Light-headedness, especially when climbing stairs or standing up
  • Fainting
  • Swollen ankles, legs, or abdomen (also called edema)
  • Loss of energy/feeling tired all the time
  • Dry cough
  • Raynaud’s phenomenon (chalky white or dusky blue fingers that may be painful and can sometimes be provoked by the cold)

In advanced stages of pulmonary hypertension, minimal activity may produce some or all of these symptoms. Patients in advanced stages may experience irregular heartbeat, a racing pulse, passing out and difficulty breathing at rest.

Sometimes these symptoms mean you have another condition, but sometimes, these symptoms mean you have pulmonary hypertension.

Risk

Factors

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

  • 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. Learn what genetics can teach us about PH
  • 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. Idiopathic PAH 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. Pregnancy is a possible risk factor suggested by registries and expert opinion. Women who already have PH and become pregnant have a much higher risk of mortality. Read more about pregnancy and PH.
  • Altitude. Living at a high altitude for years can make you more predisposed to PH. When travelling to high altitudes, your PH symptoms can be aggravated by the altitude.
  • Other diseases. Other diseases, including congenital heart disease, lung disease, liver disease and connective tissue disorders like scleroderma and lupus, can lead to the development of pulmonary hypertension. Read more about PH and associated diseases.
  • Drugs and toxins. Certain drugs, such as methamphetamines and the diet drug “fen phen,” are known to cause pulmonary hypertension.

PH

Diagnosis

Pulmonary hypertension (PH) can be difficult to diagnose in a routine medical exam because the most common symptoms of PH, such as breathlessness, fatigue and dizziness, are also associated with many other conditions. If your doctor suspects that you have PH, he or she will want to review your medical and family history, perform a physical exam and perform one or more diagnostic tests.

To determine if you have PH, 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 right-heart catheterization, which is required to confirm diagnosis.

Blood tests check the oxygen levels in the blood, they observe liver and kidney function, and they identify whether the patient has collagen vascular disease, thyroid problems, signs of infection or HIV antibodies. One test, the brain natriuretic peptide, helps to assess the strain on the heart and may also be used to monitor response to treatment.

Chest X-rays can reveal an enlarged right ventricle or pulmonary arteries. Chest X-rays can also show signs of emphysema or scarring (interstitial fibrosis) of the lungs.

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. However, an ECG alone is not enough to indicate a PH diagnosis. If your doctor performs an ECG, he or she will also perform one or more additional procedures to identify PH.

In this procedure, electrodes are placed on the patient’s skin, and a sonogram of the heart is taken. This painless procedure is often used to make a preliminary diagnosis 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. In addition, an echocardiogram may be used to monitor a patient’s condition.

These tests measure 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 may be performed to potentially identify its cause.

During this test, a patient will be asked to perform an exercise, most commonly a six-minute walk. The purpose is to identity the patient’s exercise tolerance level.

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. The doctor will review the images that are produced to evaluate the health of the lungs.

Right-Heart Catheterization

If the results of initial tests point to PH, your doctor will schedule a right-heart catheterization (commonly referred to as a “right heart cath”). Right-heart catheterization is one of the most accurate and useful tests to get a definitive diagnosis for pulmonary hypertension. This is the only test that directly measures the pressure inside the pulmonary arteries, and it should be done in all patients at least once to confirm a patient's diagnosis of PH. During the test, doctors insert a catheter (a thin rubber 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.

Vasodilator Study (Acute Vasodilator Challenge)

This test is used for patients who have already been diagnosed with pulmonary hypertension to determine how much their pulmonary blood vessels can relax over a brief period of time. Its main purpose is to screen for patients who might respond favourably to calcium channel blockers, a form of medication. The test can also help determine the patient's prognosis. With a right heart catheter in place, the patient is 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.

Types of

Pulmonary Hypertension

The term pulmonary hypertension refers to high blood pressure in the lungs. While in regular hypertension (also known as high blood pressure), the arteries throughout the body are constricted, PH affects only the blood vessels in the lungs and the right side of the heart.

PH vs. PAH: What’s the Difference?

Major Types of Pulmonary Arterial Hypertension

Other Types of Pulmonary Hypertension

Classifications of Pulmonary Hypertension

Updated Clinical

Classification of PH (Dana Point 2008)

  1. Pulmonary arterial hypertension (PAH)
  2.    Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)
  3. Pulmonary hypertension owing to left heart disease
  4. Pulmonary hypertension owing to lung disease and/or hypoxia
  5.    Chronic thromboembolic pulmonary hypertension (CTEPH)
  6. Pulmonary hypertension with unclear multifactorial mechanisms

Genetic Testing and Counselling for

Idiopathic and Familial Pulmonary Arterial Hypertension (PAH)

Consensus Statements

Issued by the Scientific Leadership CouncilA brief description of the disease and genetic testing is provided here, and sources for more extensive information are cited at the end.

n idiopathic pulmonary arterial hypertension (IPAH), formerly called primary pulmonary hypertension (PPH), there is blockage to blood flow through the small arteries in the lungs. The disease occurs more often in women and may begin at any age. Most IPAH patients have no known affected relatives, and are said to have sporadic IPAH. IPAH patients who have one or more blood relatives with IPAH are said to have familial PAH (FPAH). It is estimated that a few hundred families in the US have FPAH. Sometimes it is difficult to recognize that PAH has a familial basis, because the disease can skip generations, which happens when the parents or grandparents of a patient do not have PAH.

In most families, FPAH is caused by an inherited change (mutation) in the genetic directions for making a protein called bone morphogenetic protein receptor 2 (BMPR2). The BMPR2 protein helps regulate the growth of cells in the walls of the small arteries of the lungs. Other factors, probably genetic or environmental, are also needed to produce disease because only about 20% of individuals with a BMPR2 mutation ever develop IPAH. FPAH can occur at any age and affects women almost 3 times more often than men. Some individuals in families with a different genetic condition called Hereditary Hemorrhagic Telangiectasia (HHT) may also develop IPAH, due to a mutation in a different gene, called ALK1. Knowledge about genes that cause IPAH is still growing, so it is possible that other genes may contribute and will be discovered in the future.

Genes are units of genetic information that are passed from parents to children. Each gene contains the directions to make one or more proteins that the body needs. Genes control everything about us, including the way that our body grows and functions. All of us receive a full set of about 30,000 genes from each of our parents. Therefore, we have a pair of genes, one from each parent, to make each protein, including the BMPR2 protein.

Each normal person has a pair of BMPR2 genes in each cell in our bodies. One copy is inherited from our father and the other is inherited from our mother. The copy of the BMPR2 gene which we inherit from each parent occurs by random chance, like flipping a coin. A mutation in only one copy (from mother or father) of the pair of BMPR2 genes is enough to cause FPAH in a child.

By simple observation it can be seen that any person in the bloodline of a family with FPAH has an overall risk of about 1 in 10, or 10%, of developing FPAH during their lifetime. When a parent has a BMPR2 gene mutation, each child has a 50% chance to inherit the abnormal gene, and a 50% chance to inherit the normal gene. If a child inherits the normal gene, then that child’s risk is similar to that of the general population, which is about one in a million for developing PAH. If a child inherits the abnormal disease gene, that does not necessarily mean they will develop FPAH. The likelihood for a person with a BMPR2 mutation to develop FPAH is estimated to be about 20%, though the actual risk may be different in each family. In other words, 80 out of 100 people who inherit a BMPR2 mutation will never develop IPAH.

Identification of a genetic mutation in a patient who already has PAH does not affect their medical care, so this result has importance only to their family.

The gene for BMPR2 is very large, and many different mutations (>100) have been found in it. In each FPAH family, one specific mutation in BMPR2 is the cause of FPAH in every patient in that family, and every patient within that family has that same specific mutation. Different families have different BMPR2 mutations. Knowing which specific mutation is present in a family is important because it makes it much easier to perform genetic testing for any person in that family. Testing one part of the large BMPR2 gene for a known mutation is far easier than testing for changes in the entire gene. In other words, searching for a mistake in an entire phone book would take a very long time and the mistake could be missed, but looking up the spelling of a specific name (testing for a known mutation) is accurate and easy to do.

The cause of most sporadic IPAH is not known, but BMPR2 mutations have been found to cause sporadic IPAH in 10% to 40% of IPAH patients. Children of IPAH patients with BMPR2 mutations have the same risks as the children of individuals with familial PAH. So far, most people with sporadic IPAH do not have a detectable BMPR2 mutation.

Medical testing shows whether a person has signs of PAH at the time of testing. One simple test, an echocardiogram, is a noninvasive and painless sound wave test of the heart that is often used to screen for PAH. However, it may be expensive, is not always accurate, and does not predict whether a person will develop IPAH in the future. Genetic testing is laboratory testing of DNA, usually from a blood specimen. It searches for a mutation in a gene. The results of genetic testing can better define the actual risk for another family member to develop FPAH, especially when a BMPR2 mutation has been identified in a PAH patient in the same family. Genetic testing does not tell whether a person has any signs of PAH.

At present, BMPR2 mutations have been identified in about 80% of the families with FPAH. Information about which specific mutation is present in each family may be available from the research team. If information is not available about which particular BMPR2 mutation causes disease in a specific family, then DNA from a patient with FPAH in that family is needed to try to identify a specific mutation for their family.

By law, diagnostic testing for genetic mutations can be provided only by specially licensed clinical laboratories (CLIA approval). These regulations assure rigorous quality control at all stages of sample analysis and ensure that the test is performed by fully trained personnel. At present, most university institutional review boards (IRB) prohibit disclosure of results obtained in a research lab to unaffected family members. Thus, most research laboratories cannot reveal genetic test results for specific individuals, but the labs may provide information which they discovered about the location and type of BMPR2 mutation in a specific family.

Because there can be unexpected risks, counselling by experts (genetics counsellors) is necessary to be fully informed. Counsellors will discuss all of the benefits, drawbacks, and limitations before a person makes a decision about genetic testing.

If a family has participated in a research study, they may want to contact the coordinator or the director of the research study to determine whether a BMPR2 mutation has been identified in their family.

If a BMPR2 gene mutation has been identified, the research study coordinator can help to arrange genetic counselling. The genetics counsellor can help contact a clinical laboratory that provides genetic testing for BMPR2 mutations. The cost of testing will vary. A blood sample from a relative with IPAH or FPAH may be needed. The accuracy of testing will usually be greater than 99%.

If a BMPR2 gene mutation has not been identified, the laboratory can examine the entire gene and try to find a mutation. If a mutation is found, then this information can be used to test any family member. If a BMPR2 gene mutation cannot be found in a specific family, then genetic testing will not provide any information for unaffected family members. Another gene that has not yet been found could be responsible for PAH in that family.

If a family is not involved with a research group, they may wish to contact their primary care provider or a genetics counsellor.

This decision is very personal. After counselling, each person should decide what is in their own best interest. Some people may find it helpful to read over the “pros and cons” of testing that are listed below. These will be explained further and discussed in detail during genetic counselling.

Some possible benefits of genetic testing for familial PAH

  1. The risk for a person to develop FPAH is more accurate, which may decrease uncertainty about their health. Their children’s risk estimates are also more accurate.
  2. If a person is found to not have the BMPR2 mutation which is known to cause FPAH in their family, they may feel relieved and can safely stop medical screening for FPAH.
  3. Knowing the result may help with planning a person’s family or financial decisions.

Some possible drawbacks or limitations of genetic testing for familial PAH

  1. If a person has the BMPR2 mutation which causes FPAH in their family, they still do not know whether or when they will develop FPAH. Recommendations for medical screening are the same as before they had genetic testing.
  2. If a person has the familial BMPR2 mutation, they may feel anxious, depressed or upset.
  3. A person might have trouble buying life or health insurance if their health record showed that they inherited the familial BMPR2 mutation.
  4. A person might feel guilty because they did not inherit the familial BMPR2 mutation and escaped the disease, while their relatives suffered from FPAH.
  5. In some cases, genetic test results can cause anger, resentment, or other problems which can affect family relationships.

Genetic testing in children who are under 18 presents serious ethical issues because legally they are not able to make an informed decision. Yet genetic testing can have a profound effect on their future. For example, the results of genetic testing can alter the child’s self-image and future aspirations. It can also affect the relationship between child and parents. For these reasons, many experts strongly recommend that genetic testing in childhood be avoided except when results will provide significant medical benefits. Both the American Academy of Paediatrics and the American Society of Human Genetics have published statements regarding the ethical issues involved.

In IPAH, there is no proof so far that genetic testing in childhood improves the long term medical outcome. If a person feels strongly that testing would be beneficial for their child, they may wish to discuss their concerns with a genetic counsellor and a paediatric pulmonary hypertension physician or other expert.

Genetic testing has many important effects upon medical, social, and emotional aspects of a person’s life. For this reason, professional counselling before and after testing is very important, and is required by testing centres.

At present only a few centres offer genetic testing and professional counselling for patients with pulmonary arterial hypertension and their families.

At this time, these centres include:

  1. Columbia University
  2. LDS Hospital and the University of Utah
  3. Vanderbilt University

Learn more about Genetic Testing and PAH

Contact Details

Testing is available at the following clinical laboratories


Counselling is strongly recommended and often required prior to testing.

Columbia University Molecular Biology Laboratory

New York, NY
Mahesh M Mansukhani, MD, Director
212-305-2546

LDS Hospital

Salt Lake City, Utah
John Carlquist, PhD, Director
801-408-1028

Vanderbilt University Molecular Genetics Laboratory

Nashville, TN
Cindy Vnencak-Jones, PhD, Director
615-343-9074

Ambry Genetics Corp

Alisa Viejo, CA
James Thompson, MD, PhD, Director
949-900-5517

GINA-Genetic Information Non-Discrimination Act

Signed into law May 21, 2008 and forbids employers and insurance companies to deny employment, promotions, and/or health coverage based on genetic information.
H. R. 493 details can be found at the Library of Congress website. Click on Thomas and enter the bill number.

Policy statements

ASHG/ACMG policy statement. Ethical, legal, and psychosocial implications of genetic testing in children and adolescents. Am J Hum Genet 1995;57:1233-1241.
American Academy of Pediatrics Committee on Bioethics. Policy statement: ethical issues with genetic testing in pediatrics. Pediatrics 2001;107:1451-1455.

References and Resources

GeneTests web site. This site contains summaries of many genetic conditions including PPH. It also has contact information for genetics clinics and laboratories with links to a list of the tests that each lab performs.

National Society of Genetic Counselors Web Site. This site provides contact information for genetic counsellors in your area.

The Genetic Testing Registry. This site from the National Institutes of Health offers detailed information about genetic tests as submitted by providers.

American Lung Association

1740 Broadway
New York, NY 10019
212-315-8700
infor@lungusa.org

Columbia University

Wendy Chung, MD, PhD, Director
212-851-5313
wkc15@columbia.edu

LDS Hospital / University of Utah

Janet Williams, M.S.
Genetic Counsellor
801-408-5057
janet.williams@intermountainmail.org

Vanderbilt University

Vickie Hannig, M.S.
Genetics Counsellor
615-322-7601
Vickie.Hannig@Vanderbilt.edu

Chronic Thromboembolic

Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by old blood clots in the lungs (pulmonary embolism). In most patients who have suffered a blood clot, blood thinners are enough to restore blood flow to the lungs, improving breathing and exercise tolerance, and preventing development of pulmonary hypertension.

However, a minority of patients will not respond adequately to blood thinners, and may develop CTEPH. In these patients, problems arise not only from lung segments being obstructed by clots, but because seemingly healthy blood vessels (supplying uninvolved lung segments) may develop progressive narrowing, similar to pulmonary arterial hypertension (PAH).

Importantly, patients may develop CTEPH without any history of a blood clot. It is also possible for CTEPH to develop from multiple small clots over a long period of time, as opposed to one or two large blood clots.

The symptoms of CTEPH are non-specific, and similar to other types of pulmonary hypertension. The most common symptoms of CTEPH are shortness of breath and exercise intolerance. Less frequent symptoms include a dry cough, chest pain, and heart palpitations. As the disease progresses, symptoms of light-headedness or exercise-related dizziness may occur. Abdominal and lower extremity swelling may develop as lung pressures increase, and the right ventricle, which pumps blood into the lungs, begins to weaken.

Approximately 1% of patients with an acute pulmonary embolism will develop CTEPH. People who have very large pulmonary emboli may be at increased risk of developing CTEPH. Patients who already manifest some pulmonary hypertension at the time of diagnosis of a pulmonary embolism may also have an increased likelihood of developing CTEPH. Some underlying blood clotting disorders are more common in patients with CTEPH, though not all clotting disorders increase risk. Additionally, some chronic medical conditions, such as inflammatory bowel disease and osteomyelitis, are associated with increased CTEPH risk.

If a doctor suspects that you have CTEPH, he or she will run a number of tests. The goals of these tests are to establish whether you have CTEPH or another type of PH. If you do have CTEPH, he or she will want to determine if you are a candidate for pulmonary thromboendartectomy (PTE) surgery.

Common tests include

  1. Nuclear Scan (a.k.a. Ventilation/Perfusion Scan or V.Q. Scan). This test shows any areas in the lung that are not receiving the appropriate amount of blood flow due to blockage of the arteries by clots.
  2. Echocardiogram In this procedure, electrodes are placed on the patient’s skin and a sonogram of the heart is taken. This painless procedure is often used to make a preliminary diagnosis by estimating the pressures in the right heart and assessing how well the heart is functioning.
  3. CT scan Some patients undergo this test to look for blood clots and to evaluate the condition of the rest of the lung besides the arteries. If you get a CT scan, your veins will be injected with dye and photographed.
  4. Right-heart catheterization This is the only test that directly measures the pressure inside the pulmonary arteries, and it should be done in all patients at least once to confirm a patient's diagnosis with PH. During the test, doctors insert a catheter (a thin rubber 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.
  5. Pulmonary angiography Like a right-heart catheterization, a catheter is placed through a vein in the neck (or groin) into the pulmonary arteries. This is done by injecting dye into the arteries and taking pictures. This test will confirm if chronic blood clots are the cause of the pulmonary hypertension and if PTE surgery would improve pulmonary pressures.
  6. Coronary angiography Patients who are deemed candidates for PTE surgery and are at risk for coronary artery disease will also undergo this test to see if they have significant coronary artery disease (blockages in the arteries that supply the heart muscle with blood and oxygen). If the doctors identify significant coronary artery disease, they will typically treat it when they remove blood clots from the arteries in the lung.

The symptoms of CTEPH are quite similar to those of pulmonary arterial hypertension (PAH) and the other types of PH. Chest pain may be a more prominent feature of CTEPH, particularly in those patients who have had scarring in an area of lung from a prior blood clot. The distinguishing feature of CTEPH is that it is the only type of PH that truly has a potential “cure” for those who are eligible for PTE surgery.

The therapy of choice for operable patients is a pulmonary thromboendarterectomy, or PTE surgery, a highly specialized surgical procedure that removes chronic blood clots from the arteries in the lung.

All CTEPH patients will need to be on a blood thinner, typically warfarin, for the rest of their lives. For patients who have prominent abdominal swelling and swollen legs, diuretics may be beneficial.

PH-specific medications have been investigated in CTEPH, though the number of patients studied is much smaller than those enrolled in PAH clinical trials. These studies have confirmed the safety of several therapies, and varying degrees of benefit. Medical therapies are mainly used for inoperable patients, or for patients who have residual pulmonary hypertension after surgery. If you fall into one of these categories, your PH team will work with you to choose a medication based on your disease severity, side effects, and other relevant personal factors.


This article was written by Gautam V. Ramani, MD, Assistant Professor of Medicine at the University of Maryland School of Medicine, and Myung H. Park, MD, FACC, Director of the Pulmonary Vascular Diseases Program at the University of Maryland Heart Center.

Last reviewed: February 2012

PH

Treatment

You’ve been diagnosed with pulmonary hypertension… now what? Although there is currently no cure for pulmonary hypertension, there are treatment options available and more are on the horizon. Treatments include conventional medical therapies and oral, inhaled, intravenous (into the vein) and subcutaneous (into the skin) options. Depending on the severity of PH, heart or lung transplant may also be an option.

Remember that each patient is different. It is essential that you talk to your own doctor about what treatment options are best for you.

Please note: Not all of these treatments are available in South Africa.

Conventional Medical Therapies

Oral Treatment Options

Inhaled Treatment Options

Intravenous Treatment Options

Subcutaneous Treatment Options

Lung Transplantation

Transplant and

Pulmonary Hypertension

Lung or heart-lung transplant is a treatment option reserved for patients who are not improving on medical therapies. While transplantation can prolong survival, improve quality of life and offers a potential cure for pulmonary hypertension (PH), it also carries risk of significant complications and many factors need to be considered before going forward.

Information for Patients and Transplant Recipients

When you are no longer responding significantly to medical therapies, your physician may want to discuss the option of lung or heart-lung transplantation. Considering transplantation can be overwhelming, and the decision to get listed for transplantation is a very personal and unique process for every person. Transplantation offers a potential cure for PH, but also has the potential for significant complications.

When considering transplant, you may have questions about the process before transplant, the transplant procedure and post-transplant living. There are different issues to consider at each stage.

Language Based on Treatment Fact Sheet Issued by PHA's Scientific Leadership Council

Last reviewed in 2009

Common Questions about Transplant.

Answers about

Lung Transplantation for Pulmonary Hypertension

Part One
Overview

From the development of epoprostenol in the early 1980s to the discovery of oral and inhaled therapies over the next decades, expansion of medical treatment of pulmonary arterial hypertension (PAH) has improved survival and quality of life over the past 30 years. While research into new medical treatments is on-going, to date there is no cure. The first heart-lung transplant was performed at Stanford in 1981 for a patient with primary pulmonary hypertension, and over the next decade, single and double lung transplantation evolved. As surgical techniques and postoperative management have improved, the number of lung transplants has risen every year, reaching more than 3,000 lung transplants in 2009. With improvements in surgical treatments and pre- and post-operative management, lung transplant continues to be a viable treatment for qualified candidates whose disease is progressing despite maximal medical therapy. When considering lung transplantation, you may ask yourself one or all of the following questions. Part one in this series focuses on general questions about the transplant process.

The therapy of choice for operable patients is a pulmonary thromboendarterectomy, or PTE surgery, a highly specialized surgical procedure that removes chronic blood clots from the arteries in the lung.

All CTEPH patients will need to be on a blood thinner, typically warfarin, for the rest of their lives. For patients who have prominent abdominal swelling and swollen legs, diuretics may be beneficial.

PH-specific medications have been investigated in CTEPH, though the number of patients studied is much smaller than those enrolled in PAH clinical trials. These studies have confirmed the safety of several therapies, and varying degrees of benefit. Medical therapies are mainly used for inoperable patients, or for patients who have residual pulmonary hypertension after surgery. If you fall into one of these categories, your PH team will work with you to choose a medication based on your disease severity, side effects, and other relevant personal factors.

By and large, the procedure of choice for patients with PAH is double lung transplant. Although transplantation for PAH began with heart-lung transplant, we have found that in most cases PAH can be effectively treated through double lung transplantation alone. With the immediate changes in pulmonary artery pressures after surgery, the right ventricle is quite remarkable in its ability to heal in the months after transplant. It is important to note that there are cases in which heart-lung transplantation may be required, such as in patients who have poor heart function or irreparable structural problems that they have had since birth.

In patients who are progressing with PAH, lung transplantation can provide a promise for a chance at a better quality of life. It is important to emphasize that transplantation requires a lot of maintenance and that in essence, when undergoing transplant, a recipient trades their current medical disease for another medical condition that has a better prognosis. In all recipients post lung transplantation, overall survival at one year and five years are 79 percent and 55 percent, respectively. However, supporting a patient with PAH through transplantation is a complicated procedure, reflected in the 76 percent three-month survival in IPAH patients. When patients with IPAH survive through the first year, their overall long-term survival is significantly higher (median survival 9.5 years) compared to patients with other diagnoses (median survival 6.8 years and 6.9 years in patients with COPD and IPF, respectively). Given the technical challenges early after transplantation for IPAH, it is recommended to be cared for at a centre with experience in the PAH patient population.

While pulmonary hypertension medications are no longer needed, the transplant patient must take a combination of medications to help their body accept the lungs, as well as prevent infections. Careful medical follow up at the transplant centre is also essential to success, as transplant recipients are at risk for complications, such as rejection, infection, side-effects from medications. Quality of life can be tremendously improved when things go well, but given the regimen that goes into maintaining a lung transplant, as well as complications that may occur, life frequently is not entirely “normal.” This is discussed further in part two of this series.


By M. Patricia George, MD, University of Pittsburgh School of Medicine, and Raymond Benza, MD, West Penn Allegheny Health System, Temple University, School of Medicine, Pittsburgh, Pa.

References

  • Christie JD et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Lung and Heart-Lung Transplant Report—2011. J Heart Lung Transplantation 2011; 30:1104-22.
  • Orens JB et al. International guidelines for the selection of lung transplant candidates: 2006 update – A consensus report from the pulmonary scientific council of the International Society for Heart and Lung Transplantation. Journal of Heart and Lung Transplantation 2006; 25(7): 745-55.
  • Humbert M et al. Survival in patients with idiopathic, familial, and anorexigenassociated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156-63.

This article was first published in Pathlight Spring 2012.

Part Two
What to Expect Before and After Transplant

Part two in our series examines questions about the transplant evaluation, the process of being listed for transplant and what to expect after a transplant.

After a patient decides to undergo transplant evaluation, the patient’s physician contacts a transplant centre to arrange the outpatient evaluation week. This involves several days of outpatient testing and visits with various doctors and consultants. While some testing is performed by the patient’s primary care physician (routine cancer screening and vaccinations, for example), other testing may be done during the transplant week (lab testing, radiologic studies, catheterizations and other cardiac testing). After this is complete, the centre’s committee reviews the data and makes a recommendation on whether or not the patient is a candidate. If the patient is not yet sick enough for transplant, the committee may decide that they could be a candidate in the future but would not list the patient at this time. Instead, the centre will follow them closely every three to six months and list when their condition worsens.

The decision of when to list a patient for transplant is complicated, and we often refer to the “transplant window.” Listing too soon may potentially shorten a patient’s life due to the risk of lung transplant itself. Waiting too long may mean a patient’s heart may not recover fully with double lung transplant alone, and they may require heart-lung transplant or even be unable to be transplanted. Therefore, routine follow-up at the transplant centre, even prior to listing, is essential to determining when a patient is within the window for listing.

When patients meet criteria for transplant, the decision is made by the transplant team and patient to list the patient for transplant. Data from their evaluation week (e.g., age, diagnosis, functional status, oxygen requirement, pulmonary function testing, right heart catheterization data, carbon dioxide levels, six-minute walk distance, serum creatinine) are used to register them with the United Network for Organ Sharing (UNOS). This generates a lung allocation score (LAS), which is a number from 0 to 100 that determines where a patient is ranked on the list with respect to others. A sicker patient will have higher LAS, and thus have a higher priority in obtaining lungs when they become available.

It is known that the formula for calculating the LAS, which is used in all diagnoses (COPD, IPF, IPAH, etc.) places IPAH patients at a disadvantage. To address this, UNOS currently employs an expedited appeals process so that patients who meet certain criteria will be moved to the ninetieth percentile on the list. To meet these criteria, patients must be deteriorating on optimal medical therapy and have a right atrial pressure greater than 15 mmHg or a cardiac index less than 1.8 L/min/m2. These factors are reflective of the stability of the right ventricle, which is ultimately tied to prognosis in all PAH patients. Due to the potential for these appeals, it is important for patients to follow up routinely pre-transplant.

In addition, recent data from the REVEAL study showed that additional factors, if incorporated into the LAS calculation, would more accurately predict survival and thereby better reflect organ prioritization in patients with IPAH. These additional factors include estimates of right ventricular function, which as stated earlier, are key to determining survival in IPAH. The LAS in its current construct, more heavily weighs factors reflective of “pure lung dysfunction,” like FEV1 (a measure of airway capacity) since these predict survival better for patients with “lung diseases” like COPD. Although IPAH does occur in the lung and is hence considered a “lung disease,” these parameters are not useful in predicting survival in IPAH. This is why it was imperative to have these new “heart-related” parameters added to the LAS. This is currently under review by UNOS, and a revised formula incorporating these changes is now under consideration.

Lung transplantation involves a complete lifestyle change, and while patients no longer require PH medications, they now require a new set of medications that allows their body to accept the lungs as well as prevents infections. Careful medical follow-up is crucial to success. Lung transplantation is an active medical condition that involves routine labs, pulmonary function testing, and frequent visits to the transplant centre for the rest of a patient’s life. The transplant medications often have side effects, and patients frequently require additional medications to treat new conditions such as high blood pressure, cholesterol or diabetes. Although transplant involves active maintenance by each patient, it offers the possibility of helping patients with severe IPAH live longer and improve their quality of life. When all goes well and with close medical follow up, lung transplantation provides patients the opportunity to physically do activities they have not been able to do in years.

In summary, for many patients with PAH, lung transplantation remains a viable treatment option, and if a patient’s disease is severe or worsening, transplant evaluation should be considered. It is better to be evaluated too soon, when a patient is “too well” so that the centre can follow along and transplant can remain an option down the road should the patient’s condition worsen. While lung transplant requires a lot of medications and maintenance, it does provide the chance to improve survival and quality of life.


For more information about transplants, be sure to visit United Network for Organ Sharing. (http://www.unos.org/) By M. Patricia George, MD, University of Pittsburgh School of Medicine, and Raymond Benza, MD, West Penn Allegheny Health System, Temple University, School of Medicine, Pittsburgh, Pa.

References

  • Christie JD et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Lung and Heart-Lung Transplant Report—2011. J Heart Lung Transplantation 2011; 30:1104-22.
  • Orens JB et al. International guidelines for the selection of lung transplant candidates: 2006 update – A consensus report from the pulmonary scientific council of the International Society for Heart and Lung Transplantation. Journal of Heart and Lung Transplantation 2006; 25(7): 745-55.
  • Humbert M et al. Survival in patients with idiopathic, familial, and anorexigenassociated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156-63.
  • Pulm Circ. 2011 Apr; 1(2):182-91.Lung transplantation for pulmonary hypertension. George, MP; Champion, HC; Pilewski JM.
  • Transplantation. 2010 Aug 15; 90(3):298-305. Analysis of the lung allocation score estimation of risk of death in patients with pulmonary arterial hypertension using data from the REVEAL Registry. Benza, RL; Miller, DP; Frost, A; Barst, RJ; Krichman, AM; McGoon, MD.

This article was first published in Pathlight Summer 2012

Lung Transplantation in

Patients with Pulmonary Hypertension

DISCLAIMER

Consensus Statements
Issued by the Scientific Leadership Council

Lung transplantation is a treatment option for selected patients with pulmonary hypertension (PH) when medical therapy is no longer effective. Lung transplantation can prolong survival and improve quality of life, but some patients have significant complications and may not realize its potential benefits. Although lung transplantation offers a potential cure for PH coupled with improved quality of life, it may lead to shorter survival, on average, compared to other solid organ transplants. Potential complications include organ rejection, infections, side effects of drugs that suppress the immune system and lung transplant recipients need to be followed closely by a transplant centre that may not be close to home.

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