PRIMARY PULMONARY HYPERTENSION
Introduction
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 mmHg at rest. In the PPH patient, the mean blood pressure
in the pulmonary artery is greater than 25 mmHg at rest and
30 mmHg 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 vessels.
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.
Incidence
The true incidence of primary pulmonary hypertension 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. ____________________________________________________________
PPH is most common in young women, but anyone can get it. ____________________________________________________________
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 primary pulmonary hypertension went down to
normal levels.
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 males and females in all age ranges,
from very young children to elderly people, can get PPH. Apparently
it also affects people of all race and ethnic origins equally.
Cause
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 no animal model of the disease has been available. However,
a strain of rats was recently identified in which pulmonary
hypertension develops spontaneously.
These rats may prove useful for the study of the causes and
disease processes of PPH. ____________________________________________________________
No one knows what causes PPH. ____________________________________________________________
One thought is that some people with PPH may be hyperreactors.
This means they are unusually susceptible to agents that cause
constriction, or narrowing, of blood vessels. Indeed, people
with Raynaud's disease, a condition in which the fingers and
toes easily turn blue when cold because of an extreme reaction
of the blood vessels in their fingers and toes to cold, seem
to be more likely than others to get PPH.
PPH sometimes occurs among close family members, suggesting
there may be some inherited tendency toward hyperreactivity.
But even among brothers and sisters with PPH, the areas of the
lung affected and the course of the disease may differ greatly.
Course of the Disease
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.
Symptoms
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.
____________________________________________________________
Early symptoms usually include tiredness, shortness of breath,
and fainting. ____________________________________________________________
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.
Diagnosis
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), pulmonary emboli, or some forms of congenital
heart disease. ____________________________________________________________
A variety of tests are needed to diagnose PPH. ____________________________________________________________
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.
Electrocardiogram
The electrocardiogram (ECG) is a record of the electrical activity
produced by the heart. An abnormal ECG may indicate that the
heart is undergoing unusual stress.
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.
Echocardiogram
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.
Pulmonary Function Tests
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 flow electronically.
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.
Perfusion Lung Scan
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 lungs.
+ Right-heart Cardiac Catheterization
In right-heart cardiac catheterization, the doctor places a
thin, flexible tube, or catheter, through an arm, leg, or neck
vein in the patient, and then threads the catheter into the
right ventricle and pulmonary artery. Most important in terms
of PPH is the ability of the doctor to get a precise measure
of the blood pressure in the right side of the heart and the
pulmonary artery with this procedure. It is the only way to
get this measure, and must be performed in the hospital by a
specialist.
During catheterization, the doctor can also evaluate the right
heart's pumping ability; this is done by measuring the amount
of blood pumped out of the right side of the heart with each
heartbeat.
+ Functional Classification
Once PPH is diagnosed, most doctors will classify the disease
according to the functional classification system developed
by the New York Heart Association. It is based on patient reports
of how much activity they can comfortably undertake.
Class 1 - Patients with no symptoms of any kind, and for whom
ordinary physical activity does not cause fatigue, palpitation,
dyspnea, or anginal pain.
Class 2 - Patients who are comfortable at rest but have symptoms
with ordinary physical activity.
Class 3 - Patients who are comfortable at rest but have symptoms
with less-than-ordinary effort.
Class 4 - Patients who have symptoms at rest.
Treatment
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
primary pulmonary hypertension. 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 people do well on drugs; others may need a transplant.
____________________________________________________________
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.
+ Drugs
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 catheterizat ion.
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, results with calcium channel blocking drugs are
encouraging. By relaxing the smooth muscle in the walls of the
heart and blood vessels, these calcium blockers improve the
ability of the heart to pump blood.
A new vasodilator, prostacycline, is helping some severely
ill patients. The drug, which is now being studied in clinical
trials, imitates the natural prostacycline that the body produces
on its own to dilate blood vessels. Prostacycline also seems
to help prevent blood clots from forming.
Prostacycline is administered intravenously by a portable,
battery-operated syringe pump. The pump is worn attached to
a belt around the waist or carried in a small shoulder pack.
The medicine is then slowly and continuously pumped into the
body through a catheter placed in a vein in the neck.
Prostacycline seems to improve pulmonary hypertension and permit
more physical activity. Currently limited in supply, it is sometimes
used as a bridge to help those patients waiting for a transplant.
It may become long-term treatment for more patients once it
is released for general distribution.
+ Transplantation
The first heart-lung transplant was performed in this country
in 1981. Many of these operations were performed for patients
with primary pulmonary hypertension. 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 years.
Meanwhile, the single lung transplant is becoming another method
of transplant used in cases of PPH. This newer 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 have also been 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 to 80 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.
The Primary Pulmonary Hypertension Patient Registry
1981-1988
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 catheterization.
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
and that does not require cardiac catheterization. (END BOX)
Living with Primary Pulmonary Hypertension
With the 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, most
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.
(Photograph omitted) Most PPH patients look perfectly well.
This 40-year-old woman was diagnosed about 6 years ago.
Walking is good exercise for many patients; others choose swimming.
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 research centers.
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.
For More Information
If you are interested in receiving more information on primary
pulmonary hypertension, contact:
Office of the Director Division of Lung Diseases National Heart,
Lung, and Blood Institute National Institutes of Health Bethesda,
MD 20892
(301) 496-7208
Glossary
Angina Chest pain that originates in the heart.
Aorta Blood vessel that delivers oxygen-rich blood from the
left ventricle to the body; it is the largest blood vessel in
the body.
Atrium One of the two receiving chambers of the heart. The
right atrium receives oxygen-poor blood from the body. The left
atrium receives oxygen-rich blood from the lungs. The plural
of atrium is atria.
Blood The pressure of blood against the walls pressure of a
blood vessel or heart chamber. Unless there is reference to
another location, such as the pulmonary artery or one of the
heart chambers, it refers to the pressure in the systemic arteries,
as measured, for example, in the forearm.
Cardiac Total amount of blood being pumped by output the heart
over a particular period of time.
Catheter Thin, flexible medical tube; one use is to insert
it into a blood vessel to measure blood pressure.
Clinical Medical studies of patients that trials evaluate the
effectiveness of treatment.
Constrict Tighten; narrow.
Cyanosis A bluish color in the skin because of insufficient
oxygen.
Diastolic The lowest pressure to which blood pressure pressure
falls between contractions of the ventricles.
Dilate Relax; expand.
Dyspnea A sensation of difficulty in breathing.
Edema Swelling due to the buildup of fluid.
Endothelial The delicate lining, only one cell cells thick,
of the organs of circulation.
Fibrosis Process by which inflamed tissue becomes scarred.
Heartbeat One complete contraction of the heart.
Hyperreactive Describes a situation in which a body tissue
is especially likely to have an exaggerated reaction to a particular
situation.
Hypertension Abnormally high blood pressure.
Hypotension Abnormally low blood pressure.
Lung volume The amount of air the lungs hold.
Mean blood The average blood pressure, taking pressure account
of the rise and fall that occurs with each heartbeat. It is
often estimated by multiplying the diastolic pressure by two,
adding the systolic pressure, and then dividing this sum by
three.
Palpitation The sensation of rapid heartbeats.
Perfusion Flow.
Pulmonary Blood vessel delivering oxygen-poor artery blood
from the right ventricle to the lungs.
Pulmonary Abormally high blood pressure in the hypertension
arteries of the lungs.
Smooth muscle Muscle that performs automatic tasks, such as
constricting blood vessels.
Spirogram A record of the amounts of air being moved in and
out of the lungs.
Syncope Fainting; temporary loss of consciousness.
Systemic Relating to a process that affects the body generally;
in this instance, the way in which blood is supplied through
the aorta to all body organs except the lungs.
Systolic The highest pressure to which blood pressure pressure
rises with the contraction of the ventricles.
Vasodilator An agent that widens blood vessels.
Ventricle One of the two pumping chambers of the heart. The
right ventricle receives oxygen-poor blood from the right atrium
and pumps it to the lungs through the pulmonary artery. The
left ventricle receives oxygen-rich blood from the left atrium
and pumps it to the body through the aorta.
Source:
For additional copies, write or call:
NHLBI Information Center
P.O. Box 30105
Bethesda, MD 20824-0105
FAX: (301) 592-8563
Other information can be obtained from:
United Patients Association for Pulmonary Hypertension, Inc.
(UPAPH)
P.O. Box 24733
Speedway, IN 46224-0733
1(800) 748-7274
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