Introduction to heart transplant
The idea of replacing a bad organ with a good one has been documented in ancient mythology. The first real organ transplants were probably skin grafts that may have been done in India as early as the second century B.C. The first heart transplant in any animal is credited to Vladimer Demikhov. Working in Moscow in 1946, Demikhov switched the hearts between two dogs. The dogs survived the surgery. The first heart transplant in human beings was done in South Africa in 1967 by Dr. Christiaan Barnard; the patient only lived 18 days. Most of the research that led to successful heart transplantation took place in the United States at Stanford University under the leadership of Dr. Norman Shumway. Once Stanford started reporting better results, other centers started doing heart transplants. However, successful transplantation of a human heart was not ready for widespread clinical application until medications were developed to prevent the recipient from “rejecting” the donor heart. This happened in 1983 when the Food and Drug Administration (FDA) approved a drug called cyclosporine (Gengraf, Neoral). Before the advent of cyclosporine, overall results of heart transplant were not very good.
What is a heart transplant?Believe it or not, heart transplantation is a relatively simple
operation for a cardiac surgeon. In fact, the procedure actually
consists of three operations.
The first operation is harvesting the heart from the donor.
The donor is usually an unfortunate person who has suffered irreversible
brain injury, called “brain death”. Very often these are patients who
have had major trauma to the head, for example, in an automobile
accident. The victim’s organs, other than the brain, are working well
with the help of medications and other “life support” that may include a
respirator or other devices. A team of physicians, nurses, and
technicians goes to the hospital of the donor to remove donated organs
once brain death of the donor has been determined. The removed organs
are transported on ice to keep them alive until they can be implanted.
For the heart, this is optimally less than six hours. So, the organs are
often flown by airplane or helicopter to the recipient’s hospital.
The second operation is removing the recipient’s damaged
heart. Removing the damaged heart may be very easy or very difficult,
depending on whether the recipient has had previous heart surgery (as is
often the case). If there has been previous surgery, cutting through
the scar tissue may prolong and complicate removal of the heart.
The third operation
is probably the easiest; the implantation of the donor heart.
Today, this operation basically involves the creation of only five lines
of stitches, or “anastomoses”. These suture lines connect the large
blood vessels entering and
leaving the heart. Remarkably, if there are no complications, most
patients who have had a heart transplant are home about one week after
the surgery. The generosity of donors and their families makes organ
transplant possible.
Who needs a heart transplant?
Every year in the United States there are about 4,000 people who
could benefit from a heart transplant. Unfortunately, there are only
about 2,000 donor hearts available. Therefore, there is a careful
selection process in place to assure that hearts are distributed fairly
and to those who will benefit most from the donor heart. The heart is
just a pump, although a complicated pump. Most patients require a
transplant because their hearts can no longer pump well enough to supply
blood with oxygen and nutrients to the organs of the body. A smaller
number of patients have a good pump, but a bad “electrical conduction
system” of the heart. This electrical system determines the rate, rhythm
and sequence of contraction of the
heart muscle.
There are all kinds of problems that can occur with the conduction
system, including complete interruption of cardiac function
causing sudden cardiac death.
While there are many people with “end-stage” heart disease with
inadequate function of the heart, not all qualify for a heart
transplant. All the other important organs in the body must be in pretty
good shape. Transplants cannot be performed in patients with active
infection, cancer, or bad diabetes mellitus; patients who smoke or abuse
alcohol are also not good
candidates.
It’s not easy to be a transplant recipient. These patients need to
change their lifestyle and take numerous medications (commonly more than
30 different medications). Hence, all potential transplants patients
must undergo psychological testing to identify social and behavioral
factors that could interfere with recovery, compliance with medications,
and lifestyle changes required after transplantation.
Moreover, needing a heart and being a suitable candidate are not
enough. The potential donor heart must be compatible with the
recipient’s immune system to decrease the chance of problems with
rejection. Finally, this precious resource, the donor organ, must be
distributed fairly. The United Network for Organ Sharing (UNOS) is in
charge of a system that is in place to assure equitable allocation of
organs to individuals who will benefit the most from transplantation.
These are usually the sickest patients.
What are the results of a heart transplant?
When all potential problems are considered, the results of
transplantation are remarkably good. Keep in mind that heart failure is a
very serious and life-threatening disease. In patients with severe
forms of heart failure that require transplantation, the
one year mortality rate (that is the percent of patients who die in within one year)
is 80%. Overall, five year survival in patients with any form of heart
failure is less than 50%. Compare these outcomes with cardiac
transplant. After heart transplant, five year survival averages about
50%-60%. One year survival averages about 85%-90%.
What are the complications of a heart transplant?
One might ask, “Why is survival no better than it is after a heart
transplant?” Good question. As part of our defense mechanism to fight
off infection and even cancer, our bodies have an “immune system” to
recognize and eliminate foreign tissues such as viruses and
bacteria.
Unfortunately, our immune system also attacks transplanted organs. This
is what happens when organs are rejected; they are recognized as
foreign by the body. Rejection can be controlled with powerful
“immunosuppressive” medications. If there is not enough
immunosuppression the organ can reject acutely. Even when it seems that
there is no active rejection, there may be more subtle chronic rejection
that consists of a growth of tissue, something like scar tissue, which
causes blockage of the blood vessels of the heart. The blockage of the vessels
is the process that ultimately causes the transplanted heart to fail.
It is this chronic rejection that is the major limiting factor for the
long-term
success of heart transplantation.
Unfortunately, immunosuppression is a double-edged sword. While
immunosuppression blocks rejection, because it suppresses the immune
system, transplant patients are more susceptible to infection and
cancers of various types. Among older transplantation patients, as
survival has improved, more patients are eventually dying from cancers.
How does a heart transplant patient know if he or she is rejecting the donor organ or developing an infection?
This is not an easy question to answer because many of the
symptoms and signs of rejection and infection are the same. These include:
- weakness,
- fatigue,
- malaise (feeling lousy),
- fever, and
- “flu-like symptoms”, such as chills, headaches, dizziness, diarrhea, nausea and/or vomiting.
The more specific symptoms and signs of infection will vary greatly depending upon the site of infection within the body.
Transplant patients who experience any of these findings need to seek medical attention immediately. The
transplant physician will then do tests to determine whether the
transplanted heart is functioning normally or not. If there is no
evidence of rejection, a thorough search for infection will be performed
so that the patient can be treated appropriately.
How is rejection of the organ diagnosed and monitored?
Currently, the gold standard for monitoring rejection is the
endomyocardial biopsy. This is a simple operation for the experienced
cardiologist and can be done as an outpatient procedure. First, a
catheter is put into the jugular vein in the neck. From there, the
catheter is advanced into the right side of the heart (right ventricle)
using an x-ray method called fluoroscopy for guidance. The catheter has a
bioptome at its end, a set of two small cups which can be closed to
pinch off and remove small samples of heart muscle. The tissue is
processed and placed on glass slides to be reviewed under the microscope
by a pathologist. Based on the findings, the pathologist can determine
whether or not there is rejection.
Immunosuppressive therapy is then adjusted, for example, increased if
rejection is present. Investigators have tried to develop less invasive
methods to monitor for rejection. There is a new high-tech analysis
that can be done in a sample of blood that is very promising and much
easier for the patient than the endomyocardial biopsy. This test looks
at the expression of specific genes in cells in the blood. The amount of
expression of key genes indicates whether or not rejection is
occurring. Nevertheless, so far, no method has replaced the
endomyocardial biopsy.
Why aren’t more heart transplants done?
Cost is one reason why more heart transplants aren’t done. The cost
is always at least a few hundred thousand dollars. Not all insurers will
pay for heart transplant. The longer the recipient lives, the more
expensive the transplant. Of course, if the heart lasts longer, the
benefit is also greater to the patient and to society. It’s also not
easy to qualify for a heart transplant. One has to have a very bad heart
but an otherwise healthy body. However, the major limiting factor is
the availability of donor hearts. For many reasons, individuals and
families refuse to donate organs that could be life-saving to others.
Sometimes, even when an organ is available, there is no good match.
Other times, there is no way to get the heart to a suitable recipient in
time for the organ to still be viable.
What is the future of heart transplant?
There are several ways to help patients with end-stage heart disease.
One is to get more donors for heart transplant. This will require
teaching people the benefits of transplantation in hope of changing
society’s attitudes. Better methods of preserving organs and preventing
and treating rejection are constantly being developed. In the end,
however, there will never be enough donor hearts. Indeed, artificial
hearts already exist but have a limited life-span. Patients with
artificial hearts are at high risk of developing infection and blood
clots related to the device. Better devices are being developed all the
time. What about the use of animal organs, also
calledxenotransplantation? These organs are too “foreign” and thus the
problemswith rejection are currently insurmountable.