Pulmonary Hypertension: A Patient's Survival Guide: Fifth Edition, 2013 Revision

Copyright © 2013 Pulmonary Hypertension Association

Fifth Edition, 2013 Revision, e-Book. Chapters 4, 5, 6, 7, 8, 9, 16, 17, glossary and appendices revised and updated.

All rights reserved.

Published by the Pulmonary Hypertension Association in the United States of America.

ISBN-10: 0975898736 | ISBN-13: 978-0-9758987-3-4

Library of Congress Control Number: 2004094560

Acknowledgments & Credits

Illustration in Chapter 2: Copyright © 2002 Mayo Foundation for Medical Education and Research. All rights reserved. Used with permission from the Mayo Clinic Health Letter newsletter. • Figure in Chapter 5: Oudiz, R.J. and H.W. Farber, Dosing Considerations in the Use of Intravenous Prostanoids in Pulmonary Arterial Hypertension: An Experience-based Review, American Heart Journal, 157 (4) (625-635) April 2009, with permission from Elsevier. • Figures (3) in Chapter 8: Stehlik, J., et. al., The Registry of the International Society for Heart and Lung Transplantation: 29th Adult Lung and Heart-Lung Transplant Report — 2012, The Journal of Heart and Lung Transplantation, Vol. 31, Issue 10 (1073-1086), October 2012, with permission from Elsevier. • Chapter 9, Figure 1: D'Alonzo, Gilbert E., et. al. Survival in Patients with Primary Pulmonary Hypertension: Results from a National Prospective Registry, Annals of Internal Medicine, Vol. 15, No. 5 (343-349), September 1991. • Figures in Chapter 9: Figures 2, 3, 4, 5: Benza, R.L., et. al. An Evaluation of Long-term Survival From Time of Diagnosis in Pulmonary Arterial Hypertension From the REVEAL Registry, Chest, 142(2) (448-456), August 2012. Copyright © 2012 American College of Chest Physicians. • Chapter 9, Figure 6: Benza, R.L.,M. Gomberg-Maitland, et. al., Prognostic Factors Associated with Increased Survival in Patients with Pulmonary Arterial Hypertension Treated with Subcutaneous Treprostinil in Randomized, Placebo-Controlled Trials, The Journal of Heart and Lung Transplantation, Vol. 30, No. 9 (982-989), September 2011. • Chapter 9, Figure 7: Miyamoto, S., et. al., Clinical Correlates and Prognostic Significance of Six-Minute Walk Test in Patients with Primary Pulmonary Hypertension, American Journal of Respiratory and Critical Care Medicine, Vol. 161, No. 2 (487-492), February 2000. © 2000 The American Thoracic Society. • Chapter 9, Figure 8: Nagaya, N, et. al., Plasma Brain Natriuretic Peptide as a Prognostic Indicator in Patients With Primary Pulmonary Hypertension, Circulation, 102 (865-870), 2000. Copyright © 2000 American Heart Association, Inc. All rights reserved. • Chapter 9, Figures 11 and 12: Benza, R.L., et. al., The REVEAL Registry Risk Score Calculator in Patients Newly Diagnosed With Pulmonary Arterial Hypertension Chest, 141 (354-362), February 2012. © 2012 American College of Chest Physicians. • Chapter 9, Figure 13: Benza, R.L., et. al., Predicting Survival in Pulmonary Arterial Hypertension : Insights From the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL), Circulation, 122, 2 (164-172), June 2010. Copyright © 2010 American Heart Association, Inc. All rights reserved. • Figure in Chapter 10: Benden, C. et al., The Registry of the International Society for Heart and Lung Transplantation: Fourteenth Pediatric Lung and Heart-Lung Transplantation Report — 2011, Journal of Heart and Lung Transplantation, Vol. 30, Issue 10 (1123-1132), October 2011, with permission from Elsevier. • The Revised Clinical Classification of Pulmonary Hypertension chart in Chapter 3 was updated at the 4th WHO World Symposium on PAH in Dana Point, California. This material appeared in an article by Gerald Simonneau, MD, in the Journal of American College of Cardiology, June 2009. Copyright © 2009, with permission from Elsevier. • For the original Third Edition, Chest gave PHA special permission to use material in advance of publication (July 2004) for their guideline: Diagnosis and Management of Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guideline.

Conflict of interest disclosure statements for each of the medical professionals who contributed to the chapters revised for this Fifth Edition, 2013 Revision can be found in the Acknowledgments section.

Additional Copies

For additional copies of this book or for permission to reprint any part or to translate, contact the Pulmonary Hypertension Association, 801 Roeder Rd., Suite 1000, Silver Spring, MD 20910, U.S.A. ▪ Phone: 301-565-3004 ▪ PHA@PHAssociation.org. The book may also be ordered online at: www.PHAssociation.org/OrderSurvivalGuide or by calling 301-565-3004. The price is $10.

The Pulmonary Hypertension Association does not allow the resale of any editions of Pulmonary Hypertension: A Patient's Survival Guide and will vigorously enforce its copyright protection against anyone who violates this policy.

INTRODUCTION: The Magic of PHA & Editor's Note

CHAPTER 1: How Do I Really Know I've Got PH?

CHAPTER 2: PH: The Other High Blood Pressure

CHAPTER 3: Who Gets PH?

CHAPTER 4: Conventional Medical Treatments

CHAPTER 5: PH Drugs: Prostanoids

CHAPTER 6: Other PH Drugs

CHAPTER 7: More On PH Drugs

CHAPTER 8: Surgical Treatments

CHAPTER 9: Tell Me, Doc, How Long Do I Have?

CHAPTER 10: Children And PH: Babies, Kids, Teens and Family Planning

CHAPTER 11: Caregiving

CHAPTER 12: What to Eat When You Have PH

CHAPTER 13: Dealing with Emergencies, Doctors, Colds and Flu

CHAPTER 14: You're Not the Only One With the Blues

CHAPTER 15: The Active Life: Working, Exercising, Traveling and Living

CHAPTER 16: Insurance and Legal Matters

CHAPTER 17: Resources

Appendix 1: How to Handle Intravenous PH Medication Emergencies

Appendix 2: Pulmonary Hypertension Acronym Decoder

Appendix 3: PH Patient Organizations Around the Globe

Appendix 4: PH Drugs Chart

GLOSSARY

ACKNOWLEDGMENTS

THIS REVISION IS DEDICATED TO DOROTHY OLSON

After living brilliantly with pulmonary hypertension for more than 35 years, a founder of the Pulmonary Hypertension Association, Dorothy Olson, died in May 2013 at the age of 88. Dorothy served on PHA's Board, wrote for Pathlight, and answered the Patient-to-Patient Support Line. In recent years her medical condition was complicated by blindness, but that did not stop her from attending and speaking at PHA's biennial international PH conferences.

Back when Dorothy was diagnosed with PH there were no treatments and almost no known living PH patients. She finally got in touch with the other PHA founders: patients Teresa Knazik and Pat Paton, and Pat's sister, registered nurse Judy Simpson. In 1991, they formed the United Patients Association for Pulmonary Hypertension (UPAPH), which evolved into PHA. Dorothy's form of PH was caused by blood clots in her lungs. In 1994 she had a pulmonary thromboendarterectomy to remove the clots. The operation greatly reduced her symptoms, but her PH slowly returned. A photo of the material removed from her lungs is in the Surgical Treatments chapter.

Whatever obstacles in her path, Dorothy always found a way to reach her goal. One of her tips in Pathlight was for patients to try walking backwards when ascending a hill. I got funny looks, she reported, but it left me the breath to smile and say hello. Her smile, warmth, smart appearance, optimism and determination were — and will continue to be — an inspiration to PH patients.

YOU NEED A PH DOC, NOT JUST A BOOK

This manual is not intended to provide personal medical advice. Pulmonary hypertension is a serious condition and treatment must be individualized. Readers should seek medical advice from physicians with expertise in the field. PHA will not be responsible for readers' actions taken as a result of their interpretation of information contained in this book.

To maintain its objectivity, Pulmonary Hypertension: A Patient's Survival Guide is produced by PHA and volunteers without direct financial support from any person or group with a monetary interest in PH-related products or services. The names of some patients have been changed to protect their privacy, but all the stories are true. Because of the devastating nature of this disease, some of the patients may have since died, but their voices live on in these pages.

The formation of the Pulmonary Hypertension Association (PHA) might be the first time that patients, doctors and researchers joined together in a synergistic swarm to learn so much so fast about a fatal disease once thought to affect so few people. PHA has both generated this energy and directed it into productive channels.

This is how it began. A mere 23 years ago, in 1990, Pat Paton, a PH patient, and her sister Judy Simpson, a nurse, asked the National Organization for Rare Disorders (NORD) to help them locate other PH patients. As a result, Pat, Dorothy Olson, Teresa Knazik and Shirley Brown — all PH patients — became pen pals. Teresa began the newsletter Pathlight in May of 1990 and dubbed the group the United Patients' Association for Pulmonary Hypertension (UPAPH). Shirley became very ill and succumbed to PH (there were no FDA-approved treatments for PH back then), but the others incorporated UPAPH in November 1990. Husbands (Ed Simpson, Harry Olson, Bob Knazik and Jerry Paton) helped out with money, labor and love.

At that time, few doctors knew much about PH or even that this disease existed. Showing great foresight, UPAPH ferreted out doctors and scientists who did have expertise in the disease and enlisted their help.

UPAPH was quite a mouthful, and many people weren't sure how to pronounce the acronym. Besides, medical professionals and other non-patients now belonged to the group. So UPAPH metamorphosed into PHA, which now has more than 10,000 patient members, professional members and supporters (not counting the members of our more than 240 support groups). PHA raises millions of dollars each year to combat this dreadful disease and improve the lives of PH patients. Although PHA now has a permanent office and professional staff, patients remain the beating heart of the organization. They help with much of the work: writing and reviewing publications, organizing and staffing conferences, running support groups, answering calls to PHA's Patient-to-Patient Support Line, and serving on PHA's Board of Trustees. They also put their lives on the line to help researchers find a cure. Three more of the founders, Teresa, Dorothy and Harry, have since passed on, but Pat, Judy, Jerry and Ed remain active in PHA.

Awareness of PH has grown right along with PHA. We now believe that there are about 30,000 diagnosed patients in the United States alone, which means PH is more common than some better-known lung diseases, such as cystic fibrosis. PHA uses its medical journal, Advances in Pulmonary Hypertension; its newsletter, Pathlight; its website (www.PHAssociation.org); biennial International PH Conference; support groups; and many other means to get out the word on PH. Much of PHA's budget goes to support scientific research. Turn to Chapter 17 — Resources — to learn about everything that PHA offers to patients, family members and medical professionals.

What was once a hopeless disease is no longer so. Thanks to new medicines and increased awareness, PH patients are living longer and longer, and are being offered more (and more attractive) options to discuss with our doctors. We've got the ball rolling. Medical breakthroughs come along with increasing frequency ... as does the need for yet another revision of the Survival Guide!

Together, we can beat this thing.

Gail Boyer Hayes, 2013

(Diagnosed 1983)

Pulmonary Hypertension: A Patient's Survival Guide was first published in 1998, and has since grown in size and scope to keep up with the cutting-edge medical research and to address a number of lifestyle issues. Whether you're picking up the Survival Guide for the first time, or have followed it through its many updates, patients, family members and friends alike will benefit from the wide variety of information covered in this book.

The beauty of this manual is that it is written from a patient's perspective, with medical reasoning explained in lay terms. And all of the information in the book has been verified by medical specialists for accuracy and appropriateness. While this may not be a book to cozy up with by the fireplace or swimming pool, you may go back to it many times to satisfy your hunger for knowledge about pulmonary hypertension. We hope that most of your questions about PH will be answered, and expect that as new questions arise they will be addressed in future revisions.

The first half of the book is devoted to the mechanics of pulmonary hypertension, while the second half is devoted to lifestyle topics and resources.

Chapters that have been updated for the Fifth Edition, 2013 Revision include:

• Chapter 4: Conventional Medical Treatments

• Chapter 5: PH Drugs: Prostanoids

• Chapter 6: Other PH Drugs

• Chapter 7: More On PH Drugs

• Chapter 8: Surgical Treatments

• Chapter 9: Tell Me, Doc, How Long Do I Have?

• Chapter 16: Insurance and Legal Matters

• Chapter 17: Resources

• Appendix 1: How To Handle Intravenous PH Medication Emergencies

• Appendix 2: Pulmonary Hypertension Acronym Decoder

• Appendix 3: PH Patient Organizations Around The Globe

• Appendix 4: PH Drugs Chart

• Glossary

Ronald J. Oudiz, MD, Medical Editor

Director, Liu Center for Pulmonary Hypertension

Harbor-UCLA Medical Center

REVISED FOR THE FOURTH EDITION (SUMMER 2011) BY DEBORAH LEVINE, MD, UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO

"I have what?" is the new patient's first question. "Are you sure?" is the second. After months or years of wondering why you don't feel well, you are relieved that you finally know why: you have high blood pressure inside your lungs, and the disorder has a name: pulmonary arterial hypertension (PAH). But when your doctor told you what was wrong with you, his or her face was grave. You might have been told that without treatment, pulmonary hypertension (PH) is usually a rapidly fatal disease. If your doctor wasn't up to speed, you might even have been told there was nothing to stop PAH, and to get your affairs in order. So, along with the relief, you also feel scared, confused and angry. We've been there, we know.

With the right treatment, PAH patients can now hope to live a long time. The treatments and your options are complicated, however, so you need to know which symptoms to keep an eye on, how the disease makes you sick, what kinds of treatments are available, and how to live well in spite of PAH. Most of us like to be active participants in these decisions — it's our lives that are at stake. PHA hopes this book will raise questions to be discussed with your physician, but it is not intended to give medical advice or to set a standard for the care of pulmonary hypertension patients.

If you are a typical PAH patient, your illness may have been misdiagnosed (often more than once) before your persistence and intelligence got you into the hands of a physician familiar with PAH. Congratulations on already having leaped a major hurdle on the road to feeling better!

Because PAH symptoms are the same as the symptoms of a lot of other diseases, PAH has traditionally been diagnosed through a process of exclusion — by looking for and ruling out those other diseases. There are many doctors who still don't have PAH on their lists of possibilities and many more who have never (to their knowledge) encountered someone with the disease. Asthma and too much stress in your life are common misdiagnoses. Another reason that PAH is hard to diagnose is that no two patients seem to have exactly the same disease or symptoms.

WHAT DOES PAH FEEL LIKE?

The symptoms for all types of PAH are pretty much the same. If a doctor can find no other obvious cause for them, PAH should be suspected and a chest x-ray and echocardiogram done. Lots of things other than PAH can cause these symptoms, of course (including some conditions that themselves cause PAH). There is a direct correlation between the severity of symptoms and the progression of PAH. In other words, the worse you feel, the sicker you probably are — and vice versa. Some women find that their symptoms get a lot worse just before, or during, their menses. Very few patients have ALL of these symptoms:

• Breathlessness, also called shortness of breath, air hunger or dyspnea (pronounced either DISP-nee-uh, disp-NEE-uh, sometimes with a silent p), is the key symptom. If you peek at your chart when the doctor is out of the room and see SOB, it does not reflect your doctor's opinion of your character; it's just an abbreviation for this symptom. Some of us experience shortness of breath with exertion, during or after meals, or, if we are very severe, with just talking.

• Chest pain, also called angina pectoris (AN-jin-ah PEK-ta-ris), especially if you have it during physical exertion (there may also be a pounding in the chest during exertion). This may also feel like a pressure in your chest. About a third of PAH patients have this symptom.

• Dizziness upon standing, or climbing stairs, or straightening up from a bent position. Some patients feel dizzy just sitting in a chair.

• Fainting, or syncope (SIN-ko-pee), happens when your brain doesn't get enough oxygen and goes off the air because of a lack of blood flow to it (see the discussion later on why we pass out). Children are particularly prone to fainting upon exertion. Although patients may faint, some patients never lose consciousness.

• Chronic fatigue — if you don't know what this is, you don't have the symptom. The author hasn't the energy to explain.

• Swollen ankles and legs or edema (pronounced eh-DEE-muh) are very common. If you press into the flesh of your lower leg, it may briefly leave a dent.

• Depression may be caused by fatigue, some medications, or the (very real) stresses of coping with PAH.

• Dry cough is a symptom in many patients. Your phlegm (or sputum) may contain drops of blood (hemoptysis). It's hard to say what causes the cough: maybe an enlarged heart pressing on a nerve, or some blood pressure medicines, or increased fluid retention.

• Raynaud's (RAY-nose) phenomenon means you are prone to chilly blue fingers. This disorder is especially common in persons whose PH is associated with connective tissue disease, but some patients with idiopathic pulmonary hypertension may also get it.

Symptoms of severe PAH. If pressures inside the lungs increase, demanding more work from the heart, then symptoms may get worse: fatigue increases, there is a throbbing in the neck, a feeling of fullness in the neck and abdomen, ankles and the lower extremities swell even more, and fluid may collect in the areas around the lungs and around the abdominal organs (this is called ascites, pronounced uh-SIGH-tees). You might need more than one pillow at night to elevate your head and lungs. A few PH patients also get a buildup of fluid in the thin layer of tissue around the heart (pericardial effusion).

Breathlessness when lying down, called orthopnea (or-THOP-nee-uh), can be caused by fluid in the lungs and is a classic sign of left-heart failure. PAH patients, of course, experience right-heart failure. It is less clear why they may have orthopnea. Some patients say orthopnea feels like choking; others call it air hunger.

Other symptoms: Your liver (upper right part of your abdomen) may feel tender. Lips and fingernails may take on a bluish tint (cyanosis, pronounced sigh-uh-NO-sis). A lack of oxygen to your brain may cause memory lapses. A decrease in appetite is common; some patients lose weight and hair. Menstruation may become irregular or even stop.

A bit more about that potentially serious chest pain. Chest pain has many possible causes, some of them unrelated to the heart and lungs. It might be heartburn, a pulled muscle, bruised rib or anxiety. But it might really be your heart — or the high pressure in your pulmonary arteries, or a pulmonary embolism (a blood clot that has traveled to your lungs) — so get on the phone and tell your doc about any new or severe chest discomfort. Be as specific as you can about the nature, location and duration of the discomfort. Notice if the pain occurs when you exercise, are upset, or whatever. Some PAH patients say their chest pain is dull and deep, some say it is sharp and stabbing. Some may have uncomfortable heartbeat sensations (palpitations). It may feel as if your heart is pounding, fluttering, flip-flopping, skipping a heartbeat or racing. One woman describes palpitations as an empty elevator crashing down inside me.

Why do some of us pass out? There is more than one cause of fainting in PAH patients. (Many things unrelated to PAH can also cause fainting.) Too little blood flowing to the brain because a heart can't pump well, or has rhythm problems, or is beating too fast or too slow may cause fainting. Strong emotion, hard persistent coughing, or pain can activate the nervous system and cause fainting. Anxiety and other things can lead to hyperventilation, which can lead to fainting (a decrease in the carbon dioxide level in your blood causes vessels in the brain to constrict). If you stand still for a long time and your leg muscles aren't being used, blood may pool in your veins, your blood pressure falls, and you plop. Some PAH patients faint when they sit up or stand up too quickly if their blood pressure falls when they stand up (orthostatic hypotension). This can be caused or made worse by vasodilator drugs, which lower the blood pressure all over your body.

Exertional fainting happens when your body can't keep up with your need for extra oxygen and blood flow when you are exercising. More than one of us has passed out just beyond the top of a flight of stairs! This is why: you might faint after you stop exercising, because your blood vessels are still dilated to accommodate the extra blood flow, but your heart rate has begun to fall back. Your blood pressure falls, and so do you.

Most of us who are prone to fainting have some warning before we black out. Because of the many possible causes of fainting, whether you have warning does not usually relate to the severity of your PH. If heart rhythm problems cause you to faint, there may be no warning before you pass out. On the other hand, you usually do have warning before passing out from hyperventilation: chest discomfort, dizziness and a pins-and-needles sensation.

Tell your family not to keep you upright if you faint. It's best to be lying down, to allow the blood to get to your brain and heart. Elevating the legs while lying down can speed recovery.

The mystery of good days and bad days. A typical PAH patient has good days and bad days. Why this is so is one of the great mysteries. Some days you might dash up a flight of stairs with little trouble, but other days it's all you can do to operate the TV remote. The good days are a good sign, because they suggest that your blood vessels are still flexible, which means the potential for reversing the damage is better.

A message from Linda on the PHA discussion board vividly captures the difference between good and bad days: Have you ever had one of those days where your neck starts to build up pressure, you feel like the top of your head is being screwed on tighter and tighter, and the rest of your head is going to explode? Then your feet start to burn and ache, and your legs start to hurt, and you can't seem to get enough air in, and when you bend over to tie your shoe laces then [try] to walk out to your car, you think you might die on the way ... Then you have to walk into the gas station to pay for your gas, and on the way you see gray spots start to roll across your eyeballs and you say to yourself, 'Oh, no, not now.' ... Then there are those good days. Thank God for them. The weather is pleasant, you get up in the morning and feel well-rested ... You get the shopping done quickly, an oil change in the car, the bed sheets changed, and [mail] your packages at the post office.

FUNCTIONAL CLASSIFICATIONS OF PAH

You will hear references to the functional class of PH patients. Functional classifications for PAH are based on a modified version of the New York Heart Association (NYHA) categories of left-heart failure severity, and, collectively, are known as the World Health Organization (WHO) Functional Classification system. The NYHA and WHO classifications are almost identical and often used interchangeably.

• Class I: Patients in this category have no symptoms during ordinary physical activity. Their hearts function normally.

• Class II: Although these patients are comfortable at rest, ordinary physical activity is somewhat limited by undue breathlessness, chest pain, fatigue or near fainting.

• Class III: These patients usually have no symptoms at rest, but their physical activity is greatly limited by breathlessness, chest pain, fatigue or near fainting while doing routine things.

• Class IV: These patients are often breathless and tired even while resting and can't do any physical activity without symptoms. They show signs of right-heart failure. Under the WHO system, anyone who is prone to fainting goes into this class.

Because our medical system often fails to detect PAH in its early stages, many, if not most, patients are already in these higher classes when diagnosed because our symptoms could indicate so many more common diseases that they do not prompt doctors to think of the more unusual disease of PAH. (Patients themselves may think it is nothing particularly serious and that they are just out of shape.) Don't panic if your doctor says you are Class III or IV. With treatment, you may well drop down to a lower class.

WHAT TESTS WILL MY DOCTOR DO TO TELL IF IT'S PH?

The following are typical approaches used by PH specialists, but the diagnostic procedure will vary from doctor to doctor.

Physical exam. A routine checkup seldom discovers PH, so it often goes undiagnosed. Because the symptoms of PH (such as shortness of breath or fatigue) are common to many diseases, personal and family medical histories are important. Your doctor will use a stethoscope to listen for unusual heart sounds such as a loud pulmonic component of the second heart sound (the sound the pulmonic valve makes when it snaps shut), an ejection click, systolic murmurs (whooshing sounds due to the leakage of blood backwards across the tricuspid valve), and a gallop (a soft thud that occurs during the time the right ventricle is filling, which indicates that ventricle is weak). OK, this is pretty technical stuff, but a patient who asks, Hey, doc, hear a systolic murmur? is more likely to be treated as an intelligent participant in his or her own medical treatment.

Your doctor will also feel for a right ventricular or parasternal lift (due to an enlarged heart that can be felt just underneath the sternum as it is contracting), for an enlarged (or even throbbing) liver, and for fluid in your abdomen (ascites). Your ankles and lower legs will be checked for swelling (edema), and the jugular vein in your neck examined for swelling. The doctor will probably look at your fingers, because a long period of low concentrations of oxygen in the blood sometimes causes the nails to take on a bluish tint (cyanosis) and can cause a small bulge to form near the cuticle (clubbing).

Electrocardiogram (ECG/EKG). This may be one of the first tests done on a potential PH patient. Electrodes are taped to your chest and a recording is made of the electrical impulses of your heart. The results may indicate that the right side of the heart is thickened due to the unusual stress of high pressure. An ECG cannot, by itself, diagnose PH. You may be asked to take an ECG stress test, where you pedal a stationary bike or walk on a treadmill while you are hooked up to an ECG machine. There is a very small risk of a heart attack or serious rhythm problem during such a test, but trained people stand by ready to handle such emergencies (if your doctor thinks you'll have such problems, he/she won't order the test). There's a whole science to reading ECGs, so we won't attempt to explain the peaks and valleys in the jittery lines of the ECG.

Blood tests are done to check on how much oxygen there is in your blood (arterial blood gases), how your liver and kidneys are functioning (back pressure or limited cardiac output from severe PH can hurt them), and to find whether you have connective tissue disease (like lupus or scleroderma — more on this later), thyroid problems, signs of infections or HIV antibodies. If you have too many red blood cells (polycythemia), your body may be trying to compensate for getting too little oxygen. If a lot of carbon dioxide (CO2) is found, a reduced rate and depth of breathing (hypoventilation) may be the cause. (Hypoventilation can cause a decreased concentration of oxygen in the blood that can, in turn, cause PH or make it worse.) If your blood doesn't coagulate normally (if it's too thin, and you bleed too much) and you are not taking a blood thinner, this may suggest liver disease, as does a low albumin level.

Low oxygen saturations may or may not be found in PH patients; they are more commonly found in the sickest patients. Low oxygen saturation in a PH patient may mean the patient's heart is leaking blood from the right side to the left side, bypassing the air sacs of the lungs. It is not uncommon, however, for someone with severe PH to have normal oxygen saturation. If low saturation is found, it can be caused by several things, including the presence of interstitial lung disease (disruption of the lungs' airways) and holes in the heart, which can lead to lower oxygen saturation even if the patient has only mild PH.

The oxygen saturation of your blood can also be measured by putting a clothespin-like clip (a pulse oximeter) over your fingertip. It sends a light through your skin that lets a gizmo determine how red your blood is. More red means more oxygen in the red blood cells, the Certs-shaped blood cells that haul around the oxygen. Sometimes an overnight sleep study with a pulse oximeter will be done. Kids having such a test may say they have an E.T. finger.

Even if the blood gas or oximeter test shows normal oxygen levels, your doctor may want to take a closer look and see what happens to your oxygen saturation while you are exercising or sleeping. Many PH patients who have normal oxygen saturations at rest will require supplemental oxygen when up and about, when doing more strenuous activities, or while sleeping.

At PHA's 2002 International PH Conference, a patient asked a panel of doctors why, when she was well-saturated with oxygen, she was still short of breath. The doctors said that although a lack of oxygen can make you short of breath, shortness of breath is usually related more to right-heart failure and low cardiac output (how hard your heart can pump) than to how much oxygen is bound to the red blood cells. For example, when you start climbing a flight of stairs, even if your blood is fully loaded with all the oxygen it needs, the blood stream doesn't deliver the oxygen-rich blood to where it is needed in time to prevent breathlessness.

Chest x-rays can reveal an enlarged right ventricle and enlarged pulmonary arteries (the main pulmonary artery leading from the right ventricle of the heart to the lungs, and the first left and right branches of that artery).

If the smaller, peripheral blood vessels are not visible in the lungs in an x-ray (or angiogram), pruning of the vasculature tree might have occurred, which is a sign of many forms of PH. This means that as the vessels go further out from the right heart towards the lungs and get smaller and smaller, they taper (narrow down) more quickly than they should.

Your doctor can also look at the chest x-ray for clues that suggest certain causes of PH, like emphysema or interstitial fibrous disease of the lungs. PH caused by chronic blood clots can be suggested by triangular or wedge-shaped patches of scar tissue in the lungs downstream from suspected clots where almost no blood vessels are seen on the x-ray.

Doppler echocardiogram. This procedure (often called echo or echocardiography) is painless and is often used both to make a preliminary diagnosis and to later monitor a patient's condition. Guidelines developed regarding PH emphasize that the echocardiogram is one of the most important studies to do when PH is suspected.

Echocardiography can reveal many things about a patient's heart, such as whether PH might be present, the presence of heart defects, the heart's pumping ability, and how the valves are functioning.

This procedure is useful not only in helping to evaluate patients to see whether they may have PH, but also in monitoring how a patient's heart is responding to medications once the diagnosis is made.

Here's what to expect: a technician will put tape electrodes (patches) on your skin (see ECG, above). You will lie on your side in a darkened room while the technician uses bouncing sound waves (sonar, or ultrasound) to make a moving image of your heart (the machine works a lot like a fisherman's depth and fish finder, and is the same machine that obstetricians use to take pictures of a fetus developing in a mother's uterus). A transducer (it looks like a microphone attached to a cable) is pressed against your chest, along with some clear jelly (brr, the jelly can be cold) to enhance the transducer's ability to pick up sound waves. The microphone first sends the sound waves into your body and then picks up their echoes when they hit internal surfaces like the heart.

Because some PAH patients may have an elevated pulmonary artery pressure (PAP) only while exercising, some experts do exercise echoes while their patient is exercising, usually on a semi-erect or supine bicycle.

During the echo, a record is made of things like whether the right chambers of the heart are enlarged, the thickness of the wall of the right ventricle, any structural heart abnormalities (such as narrowed heart valves or congenital heart disease), or any abnormal amounts of fluid around the heart.

As far as is known, it does not harm the body to have these high-frequency sound waves pass through it. No x-rays are involved in this procedure. In most cases this is a non-invasive study (no needles). However, if your physician would like to get a bubble echocardiogram looking for congenital heart disease, they will place a small intravenous (IV) catheter in your arm for the procedure. For this procedure, usually agitated salt water is pushed into your veins via the IV, to look for blood flowing through places that it shouldn't (such as holes in the heart). This is called shunting.

If shunting looks likely, your doctor may order transesophageal echocardiography to get better pictures of what is going on because the esophagus (the tube from your throat to your stomach) is close to your heart. This isn't a whole lot of fun because you have to swallow a probe, a long narrow tube with a small echo microphone on the end. It's very low risk, however, and the use of sedation and local anesthesia can make you comfortable during the procedure. If it's your child undergoing this, plan a treat like ice cream afterwards — after the throat-numbing medicine wears off!

As mentioned, in PH patients, the right-sided chambers of the heart are often enlarged and weakened. The muscular walls of the right ventricle are thicker than normal because it is working too hard. If the dividing wall between the two ventricles bows into the space of the left ventricle, this is another indication that the PH is severe (see the MRI scan illustration in this chapter). A smaller-than-normal left ventricle is also a sign of severe PH.

An echo can reveal whether the right ventricle is contracting well or poorly. Cardiac output (blood flow through the heart, lungs and body) can be estimated from an echo, although the measurement is not always accurate.

The echo also measures the amount of blood flowing through the heart valves. For example, when the right ventricle of a person with PAH contracts, some blood does not go into the pulmonary artery, as it should, but leaks (jets) backwards through the tricuspid valve, into the right atrium (tricuspid regurgitation). The Doppler principle (the same principle that explains why the sound from a train's horn coming toward you is different from the sound when it is going away from you) allows an estimation to be made of how high the pressure is in your lungs. The speed with which blood cells jet backwards through the tricuspid valve depends on the pressure difference between the ventricle and atrium. This pressure difference is a reflection of the pressure in the pulmonary artery.

After the test, mathematical calculations usually allow an expert to estimate your systolic pulmonary artery pressure (PAP). It cannot be measured on everyone. Note that echocardiograms give an estimate of systolic PAP, which is often 30 to 50 percent higher than your mean PAP. To calculate your mean PAP you need to know your diastolic PAP as well, which is only obtainable from an echo if there is leakage in the pulmonary valve (much less common than tricuspid regurgitation). Even then, it is not always reliable. The only way to get exact measurements is with a cardiac catheterization (see information later in this chapter).

How does your echo compare to those of other PH patients? A study at the University of Michigan of 51 IPAH patients who had echoes found that, at the time of their diagnosis, 96 percent already had a systolic PAP of over 60 mm Hg, 92 percent had an enlarged right atrium, 98 percent an enlarged right ventricle, and 76 percent had reduced right ventricle systolic function (a weakened right heart).

Echocardiograms may be pretty accurate for many patients, but this test is not as precise as a cardiac catheterization. The cardiac catheterization is the only study that can reliably give you a diagnosis of PAH. Because echoes are less risky — and more pleasant for the patient than catheterizations — some doctors may use them to monitor a PH patient. There are situations, however, where repeated catheterizations are essential.

If an echocardiogram is done by a technician without special training and/or experience with PH patients, the results can be way off. Anecdotes abound of patients who were falsely told they did or did not have PH on the basis of poorly done echoes. This means you need to ask about the technician's training and experience (and also that of the doctor who will be interpreting the tests). An echo cannot be properly interpreted without clinical information from your specialist.

Experts can also use these echoes to look for heart disease that may have contributed to your PH. For instance, if your left atrium is enlarged, it may be that you have high pulmonary venous pressures. You might have heart valve problems or congenital heart disease.

Computed tomography (CT or CAT scans) uses a computer hooked up to an x-ray machine that rapidly rotates around you taking pictures from many angles. The computer translates these images into detailed 3-D slices of your body, revealing much that can't be seen by an ordinary x-ray. CT scans are getting better and better as a diagnostic tool, and can detect blood clots in the large arteries of your lungs, yield information about your heart, and diagnose lung disease. CT scans can sometimes find other causes for your symptoms, such as pulmonary fibrosis or emphysema (these diseases can lead to PH). A CT scan may reveal blood clot problems (although a negative scan doesn't completely rule out such clots), blocked pulmonary veins (veno-occlusive disease), tumors, inflamed vessels or mediastinal fibrosis (there's more on these causes of PH in the chapter Who Gets PH?).

Magnetic resonance imaging (MRI) scans for PAH have also improved. Like CT scans, they are noninvasive (nothing goes inside your body). Magnetic fields and radio waves produce pictures of your heart and arteries. No radiation is involved and the magnetic field is not thought to be harmful. It's painless, but expensive. The pictures look sort of like CT scans, but can often show some tissues x-rays miss.

An MRI might be ordered to look for large blood clots (although it can't totally rule them out), problems with the structure of pulmonary arteries, the size and shape of the right ventricle, the thickness of the wall of the right ventricle (which correlates, in an MRI, with mean PAP) and other relevant things. Your mean PAP can sometimes be estimated from information obtained with an MRI.

Here's what happens: you lie inside a big tube to have the test and you listen to strange noises, some of which sound like tennis shoes tumbling in a dryer (usually headphones are provided because the noises can be very loud). Some machines' walls are open on the side, and some are closed. If your facility has one of the latter and you get claustrophobic, it helps to put on a sleep mask or drape a folded towel across your eyes. Remove all metal objects before the test; the magnets used are powerful. They will rip earrings from your ears and you will not be able to pull them off the magnet. Also, don't get within 50 feet of the magnet with your credit cards — they will be instantly demagnetized. If you have a pacemaker or war shrapnel buried inside you, you can't have this test. By accompanying her daughter to such a scan, one mom learned for the first time about her daughter's body piercings.

Nuclear scan (a.k.a. ventilation/perfusion scan or V/Q scan). This is done to take a look at the plumbing in your lungs and see if the trouble could lie in the large or the small vessels. It is usually done on an outpatient basis. For the V/Q scan, a radioactive isotope is injected into a peripheral vein, and your chest is then scanned for radioactivity. This is the Q, or perfusion part of the scan. The isotope's movement in the pulmonary arteries is tracked from outside your body by special cameras (sort of like Geiger counters). Your doctor looks for areas where blood flow is blocked or reduced by clots. If none are found, it means the problem is probably in the small vessels. If significant blockages (clots) are found in the larger arteries, this can be good news, because chronic thromboembolic disease can sometimes be cured by surgery. Therefore, these clots should be looked for in all PH patients. If your V/Q scan is normal, you can usually (not always) rule out chronic thromboembolic disease.

For the V, or ventilation part of the scan, you breathe in a little radioactive gas and let it fill the airways of your lungs. The isotope's movement in the lung airways is also tracked from outside your body by special cameras. Doctors can then compare the blood flow in your lungs' arteries (Q) with the airflow through adjacent airways (V).

Occasionally, what looks like blood clots thrombo-embolic disease on a V/Q scan may turn out to be a tumor or inflammation in a pulmonary artery, something pressing on an artery, or pulmonary veno-occlusive disease (a rare disease where fibers gunk up small pulmonary veins).

Pulmonary function tests (PFTs) are breathing tests to measure how much air your lungs can hold, how much air moves in and out of them, and their ability to exchange oxygen and carbon dioxide. They may be done to assess the severity of your PH and glean clues as to its cause. In one test, you breathe in until it hurts, then expel that breath as fast and thoroughly as you can. This reveals your lung volume. The lungs of many people with PH process a slightly smaller volume of air, probably because the PH makes them stiffer. (If the volume found is less than 70 percent of normal, something other than PH itself may be causing the reduction in volume.) In another test, you breathe in and out as deep and fast as you can. It can be quite stressful, especially when the technician is yelling at you to try harder.

Pulmonary function tests can also tell if there is a blockage in the trachea, a nerve problem, or a muscular weakness that contributes to breathing difficulties, and whether you hyperventilate (blow off too much carbon dioxide, making you lightheaded).

Carbon monoxide diffusing capacity test (DLco) estimates how well oxygen is transferred from your lungs' air sacs into your blood. Because it's hard to measure this movement using oxygen itself, carbon monoxide (CO) is substituted. You breathe in a very small amount of CO, hold your breath for 10 seconds, and then exhale into a CO detector. If no CO is detected, it means it was well absorbed by your lungs (and that oxygen would be well absorbed, too). If CO is still found in the air you breathe out, then it wasn't transferred well from the lungs' air sacs into the blood vessels surrounding them. Patients with IPAH, heritable PAH or PH due to chronic thromboembolism often do not exchange quite as much oxygen as they should.

However, many lung diseases other than PAH can also cause a poor diffusing capacity. A normal test strongly suggests that a patient's PAH is not caused by pulmonary fibrosis, emphysema, etc. Your ability to exchange oxygen usually correlates with your pulmonary vascular resistance, NYHA/WHO Functional Class and your ability to do physical work, but not necessarily with the severity of your pulmonary artery pressures. Researchers at Harbor-UCLA Medical Center say that measuring DLco (and, to a lesser extent, lung volume) can help specialists evaluate patients who complain of breathlessness and fatigue. If a patient is not exchanging oxygen well, it can make a doctor think more seriously about PH, so that PH may be discovered several years earlier than it might otherwise be.

If you have limited scleroderma (see the chapter Who Gets PH?), higher PAP is generally associated with lower DLco, and so your doctor may repeat a DLco test one or more times to see if your pulmonary vessels are becoming more damaged.

Exercise tolerance tests. Your doctor might ask you to walk on a treadmill or give you a six-minute walk test to find your exercise tolerance level. A healthy person should be able to walk at least 500 meters in six minutes; someone with moderate PH might manage only 300 to 400 meters or less. Children might be asked to ride a stationary bicycle.

Because our symptoms vary from day-to-day, are these tests accurate? Doctors say that if you haven't just gotten off an airplane from a flight to Australia, or stood in line for hours the day before, the test results are reproducible to within about a 15 percent variation. If you are being tested as a participant in a drug trial, you may be given a series of exercise tolerance tests to get an accurate baseline. Your weight, physical conditioning (or lack thereof), lack of effort, and PH may all affect how well you do on the tests.

Cardiopulmonary exercise testing (CPET) is used to tell your specialist how sick you are, and also to see what effects treatments have had upon your condition. In a CPET, you breathe into a mouthpiece (maybe while riding a stationary bicycle or walking on a treadmill) while an ECG is being done. Blood pressure and oxygen level is also measured at rest and during exercise. Although not painful, it's not a glamorous procedure. Wear exercise clothes and sneakers. Because your nose is pinched shut and your mouth is clenched around a tube, you may drool a lot. The bicycle seat can be politely described as uncomfortable in spots. Ask for a gel pad if the seat is too hard. If you feel panicky about having to breathe through a mouth tube, try pretending you are snorkeling.

If you are feeling tired the day you take exercise tests, you may find them exhausting in more than one sense, and may want to arrange for somebody to drive you home afterwards.

Polysomnogram (Sleep study) is a combination of tests done if sleep apnea is suspected. (Sleep apnea is when you episodically stop breathing at night.) The tests monitor brain wave activity (with an electroencephalogram or EEG), the amount of oxygen in your blood (with a pulse oximeter), the movement of air in and out a nostril as you breathe, the up and down movement of your chest wall, and the movement of your legs.

Right-heart catheterization is one of the most accurate and useful tests for PH, and the only test that directly and accurately measures the pressure inside the pulmonary arteries. It should be done in all patients at least once, to get a definitive diagnosis (unless there is some special safety reason for not doing so). If your doctor has good reason to suspect PH, but PH didn't show up on a resting or exercise echo, then a right-heart catheterization might be called for. Because of the accuracy of this test, some doctors use it not only to diagnose, but also to monitor their PH patients. When combined with the injection of contrast dye (pulmonary angiography) it can tell whether chronic thromboembolic disease is causing your PH.

A right-heart catheterization (cardiac cath), vasodilator study (later in this chapter) and maybe an angiogram are usually done while you are awake, because the docs need your cooperation in taking deep breaths and such. You have to spend a long time lying on a hard table (thus earning the appellation patient) but most find the procedures more uncomfortable than painful. Children and some adults might need sedation to make them less anxious.

Sometimes family members and caregivers are allowed to watch a catheterization from behind a clear plastic lead screen (to protect from x-rays) while the patient has the catheter put in. Patients are covered from head to toe with sterile paper and cloth drapes — even the machines close to the patient are covered with sterile plastic. Doctors use