A diagnosis of pulmonary arterial hypertension once meant death would soon follow, but research is extending patients' life spans and raising hope for an eventual cure.
By NANCY PARADIS
Published August 10, 2004
For five years, as Penny Engel struggled with fatigue and shortness of breath, she thought she had asthma and bronchitis. That's what doctors told her. But four years ago, when she became unable to walk from one side of the room to the other, she knew something was seriously wrong.
Her doctor sent her to a cardiologist who, after many other tests, performed a catheterization of the right side of her heart. During the procedure, she heard the doctor say "She's going to die." She was sent to the Mayo Clinic in Rochester, Minn. After many more tests, Engel, 59, was told she had idiopathic (of unknown cause) pulmonary arterial hypertension.
Coincidentally, the Mayo Clinic was one of only a handful of hospitals in the country specializing in this disease in 2000. Engel is thankful she was sent there because she was able to enroll in a drug study for the first oral medication for primary pulmonary hypertension, Bosentan, now called Tracleer. This drug saved her life, she says.
Idiopathic pulmonary arterial hypertension (PAH) is a rare and incurable lung disease, affecting 1 to 2 people per million. It causes the blood pressure in the pulmonary arteries to rise above normal. For reasons physicians are only now beginning to understand, the pulmonary artery walls thicken and narrow, causing a rise in blood pressure in the arteries.. As the blood being pumped into the pulmonary arteries encounters increased resistance and the pressure rises, the heart must work harder and, over time, it becomes enlarged. With less blood circulating through the lungs, less oxygen is picked up, leading to one of the first symptoms of PAH: shortness of breath with minimal exertion. Other symptoms include fatigue, dizziness, fainting and chest pain. As the disease progresses, the ankles and legs swell and the lips and skin can take on a bluish tint. Without treatment, PAH can cause heart failure and death.
The "Energizer Bunny'
Gloria Blodgett, 69, was working as a registered nurse anesthetist at the VA hospital in the Bronx, N.Y., when she began to have fainting spells. She was diagnosed with sick sinus syndrome, a relatively uncommon syndrome that causes abnormal heart rhythms; as a result, a pacemaker was implanted.
No longer able to work in an operating room with all its equipment and electromagnetic fields, she retired and moved to Florida in 1982. She bought a house and, although she tired more easily, she was able to lead an active life and tend to her garden. In 1988, she noticed her fatigue increasing. Over time other symptoms developed.
After nearly a year of testing, Blodgett's cardiologist had a diagnosis: idiopathic PAH. By this time, the disease had progressed to an advanced stage. In 1990, most PAH patients were put on a heart-lung transplant list and told to get their affairs in order. The only drugs then available to help alleviate the symptoms were calcium channel blockers, blood thinners and diuretics.
Blodgett's cardiologist sent her to the University of Maryland in Baltimore, at that time one of only four institutions starting to treat patients with pulmonary arterial hypertension.
Today, as knowledge of the disease is gradually expanding in the medical community, Blodgett has found a physician familiar with the disease closer to home, Dr. John Swisher, a pulmonologist in Sarasota.
Since her diagnosis, other drugs have been added to Blodgett's regimen: Flolan five years ago and a high-dose Viagra a year ago. "People are being diagnosed in earlier stages now," she said, "when the progression can be halted." Still, having had many close calls, she feels lucky to be alive.
"My sister calls me the Energizer Bunny," she said.
Misdiagnosis is not uncommon in PAH patients because the disease shares many of the same symptoms found in other conditions that affect the heart and lungs. Patients are often diagnosed with asthma, chronic bronchitis, chronic obstructive pulmonary disease, blood clots in the lungs or congestive heart disease. By the time pulmonary hypertension is accurately identified, the disease often has progressed to a late stage. However, new drugs now allow some patients to survive for 10 to 20 years or longer.
Living with PAH now an option
The daily schedules of patients with PAH are dictated by their disease, particularly for those in whom it has progressed to an advanced stage. Every afternoon, Blodgett must prepare her next 24-hour supply of Flolan, the drug on which her life depends. She mixes the powdered drug with a diluting agent and injects it into a sterile cassette. Unstable at room temperature, the drug solution must be kept cold once mixed. The cassette, surrounded by ice packs, is inserted into a pump that she wears in a pack around her waist. The Flolan is infused, via a catheter, directly into the heart through a permanent port site in her upper chest. Because of its short half life of three to five minutes, the drug must be infused continuously. Accidentally pulling out the catheter or any other inadvertent interruption could be fatal, so Blodgett always has a spare pump and filled cassette nearby.
Flolan is just one of Blodgett's life lines; the other is an oxygen tank. At home, she is tethered to one of two large oxygen tanks by a 50-foot tube that allows her to move about her apartment. Leaving the apartment requires a portable tank. Walking more than a short distance causes the oxygen saturation levels in her blood to drop dangerously, so she uses a scooter to get from her apartment to her van. Another scooter stays in the van for the short trips around town that her doctor allows her to make.
In 1987, there were only 50 diagnosed cases of PAH, no hope and not much knowledge or research. Three PAH patients who had found each other through the National Organization for Rare Disorders sat around a kitchen table in Indiantown with a common purpose of reaching out to others affected by this disease. Soon joined by a fourth, their goals were to help patients and caregivers cope, provide networking and support-group opportunities, and assist in locating doctors and medical facilities treating pulmonary hypertension. The seeds for the nonprofit organization now known as the Pulmonary Hypertension Association were sown.
From the beginning, the patient-driven association has been active in promoting research and educating both the medical community and the public. At the association's Sixth International PHA Conference, held in late June in Miami, about 900 conference attendees - doctors, researchers, patients, caregivers and drug company representatives - shared medical and scientific advances as well as stories of survival, courage and hope, while they remembered those who had succumbed to the disease.
For Dr. C. Gregory Elliott from Latter-Day Saints Hospital in Salt Lake City, the message remains that pulmonary arterial hypertension is a serious condition that may be responsible for common symptoms like breathlessness or unusual fatigue.
Dr. Charles Burger, a pulmonologist with the Mayo Clinic in Jacksonville, said present research suggests this disease may one day be curable.
"In the interim we're managing the disease much more effectively than five years ago," he said, through patient advocacy and education, research and the availability of more than one option for treatment. "We're pushing the envelope."
