pulminary, pulmanary, hypertention
Primary, or unexplained, pulmonary
hypertension (PPH) is a rare lung disorder in which the blood pressure in the
pulmonary artery rises far above normal levels for no apparent reason. The
pulmonary artery is the blood vessel carrying oxygen-poor blood from the right
ventricle, one of the pumping chambers of the heart, to the lungs. In the lungs,
the blood picks up oxygen and then flows to the left side of the heart, where it
is pumped by the left ventricle to the rest of the body through the aorta.
Hypertension is the medical term for an abnormally high blood pressure.
Normal mean pulmonary-artery pressure is approximately 14 mm Hg at rest. In the
PPH patient, the mean blood pressure in the pulmonary artery is greater than 25
mm Hg at rest and 30 mm Hg during exercise. This abnormally high pressure
(pulmonary hypertension) is associated with changes in the small blood vessels
in the lungs, resulting in an increased resistance to blood flowing through the
This increased resistance, in turn, places a strain on the right ventricle,
which now has to work harder than usual against the resistance to move adequate
amounts of blood through the lungs.
The true incidence of PPH is unknown. The
first reported case occurred in 1891, when E. Romberg, a German doctor,
published a description of a patient who, at autopsy, showed thickening of the
pulmonary artery but no heart or lung disease that might have caused the
condition. In 1951, when 39 cases were reported by Dr. D.T. Dresdale in the
United States, the illness received its name.
Between 1967 and 1973, a 10-fold increase in unexplained pulmonary
hypertension was reported in central Europe. The rise was subsequently traced to
aminorex fumarate, an amphetamine-like drug introduced in Europe in 1965 to
control appetite. Only about 1 in 1,000 people who took the drug developed PPH.
When they stopped taking the drug, some improved considerably; in others, the
disease kept getting worse. Once aminorex was removed from the market, the
incidence of PPH went down to normal levels.
More recently, in the United States and France, several cases of PPH have
been associated with the appetite suppressants, fenfluramine and
In the United States it has been estimated that 300 new cases of PPH are
diagnosed each year; the greatest number are reported in women between the ages
of 21 and 40. Indeed, at one time the disease was thought to occur among young
women almost exclusively; we now know, however, that men and women in all age
ranges, from very young children to elderly people, can develop PPH. Apparently
it also affects people of all racial and ethnic origins equally.
There may be one or more causes of PPH; however,
all remain unknown. The low incidence makes learning more about the disease
extremely difficult. Studies of PPH also have been difficult because a good
animal model of the disease has not been available.
Researchers think that in most people who develop PPH the blood vessels are
particularly sensitive to certain internal or external factors and constrict, or
narrow, when exposed to these factors. For example, people with Raynaud's
disease seem more likely than others to develop PPH; Raynaud's disease is a
condition in which the fingers and toes turn blue when cold because the blood
vessels in the fingers and toes are particularly sensitive to cold. Diet
suppressants, cocaine, HIV, and pregnancy are some of the factors that are
thought to trigger constriction, or narrowing, in the pulmonary artery.
In about 6 to 10 percent of cases, PPH is familial; that is, it is inherited
from other family members. The familial form of PPH is similar to the more
common form of the disease, sometimes referred to as "sporadic" PPH.
|Normal small pulmonary artery with typically thin
|Some of the changes that can occur in primary
|Wall of small pulmonary artery thickens.
|Fibrous, or scarred, tissue appears on inner wall of
small pulmonary artery.
|Bands of scarred tissue build up on inner wall of
small pulmonary artery, substantially narrowing the blood vessel.
Researchers believe that one of
the ways PPH starts is with injury to the layer of cells (the endothelial cells)
that line the small blood vessels of the lungs. This injury, which occurs for
unknown reasons, may bring about changes in the way the endothelial cells
interact with smooth muscle cells in the vessel wall. As a result, the smooth
muscle contracts more than normal and thereby narrows the vessel.
The process eventually results in the development of extra amounts of tissue
in the walls of the pulmonary arteries. The amount of muscle increases in some
arteries, and muscle appears in the walls of arteries that normally have no
muscle. With time, scarring, or fibrosis, of the arteries takes place, and they
become stiff as well as thickened. Some vessels may become completely blocked.
There is also a tendency for blood clots to form within the smaller arteries.
In response to the extra demands placed on it by PPH, the heart muscle gets
bigger, and the right ventricle expands in size. Overworked and enlarged, the
right ventricle gradually becomes weak and loses its ability to pump enough
blood to the lungs. Eventually, the right side of the heart may fail completely,
resulting in death.
In general, researchers find there is no
correlation between the time PPH is thought to have started, the age at which it
is diagnosed, and the severity of symptoms. In some patients, especially
children, the disease progresses fairly rapidly.
The first symptom is frequently tiredness, with many patients thinking they
tire easily because they are simply out of shape. Difficulty in breathing
(dyspnea), dizziness, and even fainting spells (syncope) are also typical early
symptoms. Swelling in the ankles or legs (edema), bluish lips and skin
(cyanosis), and chest pain (angina) are among other symptoms of the disease.
Patients with PPH may also complain of a racing pulse; many feel they have
trouble getting enough air. Palpitations, a strong throbbing sensation brought
on by the increased rate of the heartbeat, can also cause discomfort.
Some people with PPH do not seek medical advice until they can no longer go
about their daily routine. The more severe the symptoms, the more advanced the
disease. In these more advanced stages, the patient is able to perform only
minimal activity and has symptoms even when resting. The disease may worsen to
the point where the patient is completely bedridden.
PPH is rarely picked up in a routine medical
examination. Even in its later stages, the signs of the disease can be confused
with other conditions affecting the heart and lungs. Thus, much time can pass
between the time the symptoms of PPH appear and a definite diagnosis is made.
PPH remains a diagnosis of exclusion. This means that it is diagnosed only
after the doctor finds pulmonary hypertension and excludes or cannot find other
reasons for the hypertension, such as a chronic obstructive pulmonary disease
(chronic bronchitis and emphysema), blood clots in the lung (pulmonary
thromboemboli), or some forms of congenital heart disease.
The first tests for PPH help the doctor determine how well the heart and
lungs are performing. If the results of these tests do not give the doctor
enough information, the doctor must perform a cardiac catheterization. The
procedure, discussed below, is the way the doctor can make certain that the
patient's problems are due to PPH and not to some other condition.
The electrocardiogram (ECG) is a record of the electrical activity produced
by the heart. An abnormal ECG may indicate that the heart is undergoing
In addition to the usual ECG performed while the patient is at rest, the
doctor may order an exercise ECG. This ECG helps the doctor evaluate the
performance of the heart during exercise, for example, walking a treadmill in
the doctor's office.
In an echocardiogram, the doctor uses sound waves to map the structure of
the heart by placing a slim device that looks like a microphone on the
patient's chest. The instrument sends sound waves into the heart, which then
are reflected back to form a moving image of the beating heart's structure on
a TV screen. A record is made on paper or videotape. The moving pictures show
how well the heart is functioning. The still pictures permit the doctor to
measure the size of the heart and the thickness of the heart muscle; in the
patient with severe pulmonary hypertension, the still pictures will show that
the right heart is enlarged, while the left heart is either normal or reduced
in size. Echocardiograms are helpful in excluding some other causes of
pulmonary hypertension and can be useful in monitoring the response to
A variety of tests called pulmonary function tests (PFTs) evaluate lung
function. In these procedures, the patient, with a nose clip in place,
breathes in and out through a mouthpiece. The patient's breathing displaces
the air held in a container suspended in water. As the container rises and
falls in response to the patient's breathing, the movements produce a record,
or spirogram, that helps the doctor measure lung volume (how much air the
lungs hold) and the air flow in and out of the lungs. Some devices measure air
A mild restriction in air movement is commonly seen in patients with PPH.
This restriction is thought to be due, in part, to the increased stiffness of
the lungs resulting from both the changes in the structure and the high blood
pressure in the pulmonary arteries.
A perfusion lung scan shows the
pattern of blood flow in the lungs; it can also tell the doctor whether a
patient has large blood clots in the lungs. In the perfusion scan, the doctor
injects a radioactive substance into a vein. Immediately after the injection,
the chest is scanned for radioactivity. Areas in the lung where blood clots
are blocking the flow of blood will show up as blank or clear areas.
Two patterns of pulmonary perfusion are seen in patients with PPH. One is a
normal pattern of blood distribution; the other shows a scattering of patchy
abnormalities in blood flow.
A major reason for doing a perfusion scan is to distinguish patients with
PPH from those whose pulmonary hypertension is due to blood clots in the
Some patients do well by taking medicines
that make the work of the right ventricle easier. Anticoagulants, for example,
can decrease the tendency of the blood to clot, thereby permitting blood to flow
more freely. Diuretics decrease the amount of fluid in the body, further
reducing the amount of work the heart has to do.
Until recently, nothing more could be done for people who have PPH. However,
today doctors can choose from a variety of drugs that help lower blood pressure
in the lungs and improve the performance of the heart in many patients.
Some patients also require supplemental oxygen delivered through nasal prongs
or a mask if breathing becomes difficult; some need oxygen around the clock. In
severely affected cases, a heart-lung, single lung, or double lung
transplantation may be appropriate.
Doctors now know that PPH patients respond
differently to the different medicines that dilate, or relax, blood vessels
and that no one drug is consistently effective in all patients. Because
individual reactions vary, different drugs have to be tried before chronic or
long-term treatment begins. During the course of the disease, the amount and
type of medicine may also have to be changed.
To find out which medicine works best for a particular patient, doctors
evaluate the drugs during cardiac catheterization. This way they can see the
effect of the medicine on the patient's heart and lungs. They can also adjust
the dose to reduce the side effects that may occur--for example, systemic low
blood pressure (hypotension); nausea; angina; headaches; or flushing.
To determine whether a drug is improving a patient's condition, both the
pulmonary pressure and the amount of blood being pumped by the heart (the
cardiac output) must be evaluated. A decrease in pulmonary pressure alone, for
example, does not necessarily mean that the patient is recovering; cardiac
output must either increase or remain unchanged. The most desirable response
is a decrease in pressure and an increase in cardiac output. Once the patient
has reached a stable condition, he or she can go home, returning every few
weeks or months to the doctor for followup.
At present, approximately one-quarter to one-half of patients can be
treated with calcium channel blocking drugs given by mouth. By relaxing the
smooth muscle in the walls of the heart and blood vessels, these calcium
channel blockers improve the ability of the heart to pump blood.
A vasodilator, prostacyclin, is helping some severely ill patients who are
unresponsive to treatment with calcium channel blockers. The drug, which has
been studied in clinical trials, imitates the natural prostacyclin that the
body produces on its own to dilate blood vessels. Prostacyclin also seems to
help prevent blood clots from forming.
Prostacyclin is administered intravenously by a portable, battery-operated
pump. The pump is worn attached to a belt around the waist or carried in a
small shoulder pack. The medication is then slowly and continuously pumped
into the body through a permanent catheter placed in a vein in the neck.
Protstacyclin seems to improve pulmonary hypertension and permit more
physical activity. It is sometimes used as a bridge to help those patients
waiting for a transplant, while in other cases it is used for long-term
The first heart-lung transplant was
performed in this country in 1981. Many of these operations were performed for
patients with PPH. The survival rate is the same as for other patients with
heart-lung transplants, about 60 percent for 1 year, and 37 percent for 5
The single lung transplant is the most common method of transplant used in
cases of PPH. This procedure, in which one lung--either the left or right--is
replaced, was first performed in 1983 in patients with pulmonary fibrosis.
Double lung transplants are also done to treat PPH, but are less common than
the single lung transplant for treatment of PPH.
There are fewer complications with the single lung transplant than with the
heart-lung transplant, and the survival rate is on the order of 70 percent for
1 year. A surprising finding is the remarkable ability of the right ventricle
to heal itself. In patients with lung transplants, both the structure and
function of the right ventricle markedly improve. Complications of
transplantation include rejection by the body of the transplanted organ, and
infection. Patients take medications for life to reduce their body's immune
system's ability to reject "foreign" organs.
In 1981, the National Heart, Lung, and Blood Institute (NHLBI)
established the first PPH-patient registry in the world. The registry
followed 194 people with PPH over a period of at least 1 year and, in some
cases, for as long as 7.5 years. Much of what we know about the illness
today stems from this study.
At the time the patients enrolled in the registry, 75 percent were in
functional classes 3 or 4. They had an average mean pulmonary artery
pressure three times the normal, an abnormally high pressure in the right
side of the heart, and a reduced cardiac output. In making the diagnosis
of PPH, investigators found no complications arising from cardiac
The study findings show that pulmonary artery pressure in patients who
had symptoms for less than 1 year was similar to that in patients who had
symptoms for more than 3 years. Researchers also found that patients whose
only symptom was difficulty in breathing upon exercise already had very
high pulmonary artery pressure. This suggests that the pulmonary artery
pressure rises to high levels early in the course of the disease.
No correlations could be found between the cause of PPH and cigarette
smoking, occupation, place of residence, pregnancy, use of appetite
suppressants, or use of prescription drugs, including oral contraceptives.
This study was designed to serve only as a registry, so it was not
possible to evaluate the effectiveness of treatment.
Because we still do not understand the cause or have a cure for PPH,
NHLBI remains committed to supporting basic and clinical studies of this
illness. Basic research studies are focusing on the possible involvement
of immunologic and genetic factors in the cause and progression of PPH,
looking at agents that cause narrowing of the pulmonary blood vessels, and
identifying factors that cause growth of smooth muscle and formation of
scar tissue in the vessel walls. Most important is finding a reliable way
to diagnose PPH early in the course of the disease that does not require
cause of primary pulmonary hypertension still unknown, there is at present no
known way to prevent or cure this disease. However, many patients report that by
changing some parts of their lifestyle, they can go about many of their daily
tasks. For example, they do relaxation exercises, try to reduce stress, and
adopt a positive mental attitude.
People with PPH go to school, work at home or outside the home part-time or
full-time, and raise their children. Indeed, many patients with PPH do not look
sick, and some feel perfectly well much of the time as long as they do not
strain themselves physically.
Walking is good exercise for many patients. Some patients with advanced PPH
carry portable oxygen when they go out; patients who find walking too exhausting
may use a wheelchair or motorized scooter. Others stay busy with activities that
are not of a physical nature.
For the patient who lives at a high altitude, a move to a lower
altitude--where the air is not so thin, and thus the amount of oxygen is
higher--can be helpful. Medical care is important, preferably by a doctor who is
a pulmonary vascular specialist. These specialists are usually located at major
PPH patients can also help themselves by following the same sensible health
measures that everyone should observe. These include eating a healthy diet, not
smoking, and getting plenty of rest. Pregnancy is not advised because it puts an
extra load on the heart. Oral contraceptives are not recommended, and other
methods of birth control should be used.
Most doctors and patients agree that it is important for both patient and
family to be as informed as possible about PPH. In this way everyone can
understand the illness and apply that information to what is happening. In
addition to family and close friends, support groups can help the PPH patient.
Keeping on Top of Your Condition
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