Thirty years ago professor Philip
Oyer, MD, began testing a mechanical pump designed to give failing hearts
a longer life. A surgery resident at Stanford at the time, Oyer tested
it in calves to help the device’s developers determine its optimal
size, shape and pumping power.
In those early days, Oyer wondered at the likely success of a machine
designed to replace a left ventricle — the heart’s main pumping
chamber. “Initially the thing would only run for half an hour before
something or other would break,” recalls Oyer, now a professor of
cardiothoracic surgery at Stanford.
But the staggering need for end-stage heart failure therapies urged him
on. As many as 100,000 people per year in the United States can benefit
from treatment for end-stage heart failure; yet inadequate availability
of donor organs limits heart transplants to fewer than 3,000 annually
in this country. Could a mechanical pump allow patients facing heart failure
to survive until a donor heart finally came their way?
Today, Oyer and his fellow Stanford cardiothoracic surgeons know the answer
is yes. Indeed, the line of research Oyer helped launch in the 1970s has
led to the development of a family of machines called left ventricular
assist devices, or LVADs, designed to plug into a damaged heart, boost
its output and help patients survive and possibly even recover from end-stage
heart failure.
“The LVAD we’d been testing, the Novacor, became the leader
of the pack and was ready for patients in 1984,” says Oyer. In August
of that year he implanted the device in a patient as part of the first
success at using a mechanical device as a “bridge” to support
a human in end-stage heart failure until a heart transplant was possible.
The patient depended on the implanted pump for two weeks before transplant;
17 years later he’s still alive. Since that first surgery, more
than 4,000 end-stage heart failure patients worldwide have received LVADs.
Still, the need to help patients survive end-stage heart failure continues.
Are LVADs the best solution? That’s the belief of Oyer and Stanford’s
other LVAD surgeon, Robert C. Robbins, MD, assistant professor of cardiothoracic
surgery. In fact, they are poised to begin testing new mechanical devices
to assist ailing hearts — including a miniaturized version that,
because of its small size, should cause less trauma during implantation.
Robert C. Robbins
Solutions other than LVADs do exist, however. The unmet need has fueled
research into transplantation from animals as well as the development
of permanently implantable devices. “A lot of advances have been
made in xenotransplantation,” says Robbins. “Particularly
with transgenic pigs — pigs bred with certain human genes to prevent
rejection. But I think mechanical support, which has worked great as a
bridge to transplant, is most likely to serve as a long-term solution.”
Some surgeons, though none at Stanford, are pursuing a more radical treatment
for heart failure: total artificial hearts. This approach requires removal
of a damaged heart and replacement by a machine. In 1982, surgeon William
DeVries, MD, at the University of Utah, implanted the first total heart,
the infamous Jarvik-7; patient Barney Clark was tethered to the large
machine and died 112 days after from multiple strokes and infections caused
by the device. Later patients had similar experiences.
“Obviously that pump didn’t become very useful, although a
permutation of it is still used today at a couple centers,” notes
Oyer, the Roy B. Cohn-Theodore A. Falasco Professor in Cardiothoracic
Surgery.
More recently, total artificial heart efforts were in the news with the
successful implantation of the AbioCor artificial heart in July at the
Jewish Hospital in Louisville, Ky. Yet even as this first self-contained,
battery-powered heart was being implanted, Robert Jarvik, MD, inventor
of the Jarvik-7, called the new technology unnecessary. These days even
Jarvik has joined the “LVAD camp,” jokes Oyer.
Stanford’s cardiothoracic surgeons say that for now, they’re
sticking with LVADs. Their reasoning: first-generation LVADs such as the
HeartMate, made by Thoratec Corp., and Novacor, made by WorldHeart, are
the most tested and reliable devices for supporting a failing heart until
a transplant is possible.
These electro-mechanically driven pumps are slightly larger than a human
heart and weigh about 550 grams — about as much as a pint of milk.
Surgeons implant the device in a pocket they create above the muscle and
below the skin within the abdominal wall.
During placement, they tunnel two conduits through the diaphragm from
the pump to the heart, one leading to a hole cored in the apex of the
left ventricle, the other to the ascending aorta. A tube with about the
same diameter as a fountain pen carries control and power wires out through
the patient’s skin to battery packs. The batteries and controller
weigh about six pounds and can be tucked into a vest with pockets, worn
on a belt or carried in a shoulder bag. The patient can also run the device
by plugging it into a wall socket.
Philip E. Oyer: The success of the pumps he helped test came as a pleasant
surprise.
The success of the Novacor, much like the HeartMate, lies in its solid,
workhorse simplicity, says Oyer. Electrical energy is used to energize
two magnets, drawing them together and causing pusher plates to squeeze
closed the blood sac and eject the blood held inside. Valves inside the
pump keep blood from flowing backwards. Blood refills the chamber, drawn
by its lower pressure, at the rate of the patient’s venous return.
Stanford’s center leads northern California in numbers of LVADs
implanted as a bridge to transplant, with 15 to 20 patients a year. The
center offers the three primary LVADs in use: the Thoratec, the Novacor
and since July the HeartMate.
“The Novacor and HeartMate are pretty large pumps,” says Julie
Shinn, clinical nurse specialist. “Not every body size can handle
them — in fact most women can’t and children can’t.
Smaller people need a pump they can carry outside the body, which is why
we offer the Thoratec, an external pump. It can also support both ventricles,
so we use it in cases when that is needed.”
The HeartMate and Novacor have advantages too. The HeartMate, the LVAD
most commonly used in the United States, has a lower incidence of stroke,
and patients on it are not required to take anti-coagulants beyond aspirin.
Still, the longest period of LVAD support has occurred on the Novacor
— almost four years. “It’s probably the most reliable
long-term durability device there is,” says Oyer.
Typically a patient is on the brink of death when the decision is made
to implant an LVAD. At Stanford these people have ranged in age from 10
to 65, most already listed as transplant candidates. “What happens
is a patient’s heart will destabilize,” says Shinn. “They
end up in the coronary care unit on respirators. They’ve become
refractory to their medical therapy and have only days to live. Before
they have secondary organ dysfunction, we want to put a pump in these
patients. It’s not a simple operation, so the thing is not to jump
in there with the operation too quickly — but also not to wait too
long.”
“Only about 70 percent to 75 percent of people who get a device
as a bridge to transplant will actually get a transplant,” says
Robbins. “During convalescence the others die, either immediately
or from some complication down the road or they just aren’t transplanted
for whatever reason. But for those transplanted, the results are better
when they’ve been on a ventricular assist device.”
Julie Shinn: Shinn helps heart failure patients survive
until transplants are possible.
“You’re basically providing a good heart,” says Shinn.
The device raises the blood pressure of patients, enabling their kidneys
to become suffused with blood, so patients are able to make urine. Their
brains get better blood flow so they are no longer continually addled.
Patients generally are able to rise and walk within two or three days.
They recover nutritionally, gain good weight and the symptoms of heart
failure recede. In contrast, patients going directly from the ICU to transplantation
without LVADs are often debilitated and weak and less-than-optimal surgical
candidates.
Currently at Stanford, heart disease patients who are not transplant candidates
have the option of receiving the Novacor pump as part of a trial to evaluate
its long-term use. The multicenter study compares survival rates and quality
of life between end-stage heart failure patients who receive the Novacor
and those supported by the best available drug therapies.
The trial and others like it will help researchers decide how best to
meet the great need for end-stage heart failure therapies. One problem
with total artificial hearts is that their relatively larger surface area
heightens the likelihood of the formation of blood clots, resulting in
an increased risk of complications such as strokes, says Oyer. “The
other thing is the potential for infection, because you’ve got all
that hardware in there, as was the case with the original Jarvik total
heart,” he adds.
Still, an attraction persists for a completely implantable device. Since
1999 a totally implantable LVAD, called the Arrow Lionheart, is being
offered by a group led by Walter Pae, MD, of Penn State. But this device
has liabilities as well.
According to Robbins, who has a neighborly Mississippi accent and a youthful
enthusiasm, “That thing is like putting a Volkswagen engine in somebody.”
Part of the problem is that the air that moves the pusher plates to pump
the blood has to be displaced somewhere. Other pulsatory LVADs displace
the air outside the body through a drive line and vent. But a totally
implantable device such as the Arrow Lionheart requires a volume compensator
— a kind of balloon.
“That takes up a large part of the volume for the lung on the left
side,” says Robbins. “And then the pump and all the controllers
and connectors are just huge. Progress is being made to reduce the controller’s
size but, still, that’s a lot of hardware to carry around just to
get a totally implantable device. We considered the Arrow Lionheart, but
what we’re really interested in next are the axial flow pumps.”
The flow or “spinner” pumps are essentially high-speed turbines
that run at 5,000 to 10,000 rpm and are designed with vents like jet engines.
They don’t employ the pulsing motion of conventional LVADs —
and so don’t require a volume compensator — but move blood
continuously as a rotating blade in a jet engine moves air. Also, they’re
advantageously small — the size of a human thumb; to implant one
requires much less invasion than other LVAD surgeries. For instance, a
Novacor implant requires an incision from the top of the breastbone to
the umbilicus. In the case of a total artificial-heart implant, the breastbone
is divided to take out the heart. In contrast, the minute axial flow pump
can be implanted through a small incision under the breast.
“It’s just a tiny pump with a very thin drive line that comes
out like a small electrical wire — as opposed to this big garden
hose with the Novacor and HeartMate,” says Robbins. “You can
use it in smaller patients, implant it through really small incisions
and if you’re using it as a bridge to transplant, it should work
just fine. They’re probably not going to be the total answer, though,
because they have blood-lubricated bearings, which make their longevity
somewhat questionable.”
At present, three competing companies have provided the flow pumps to
a few select sites. “One of them has DeBakey's name on it —
it’s been used for a couple years in Europe,” says Oyer, referring
to heart bypass pioneer Michael DeBakey, MD, cardiovascular surgeon and
chancellor emeritus at the Baylor College of Medicine in Houston. “Jarvik
has another one, being used at the Texas Heart Institute. The DeBakey
spinner turbine pump has problems. It breaks some, and blood clots on
it some. The Jarvik spinner pump has only 10 patients so far. The initial
reports are really glowing — just as the initial reports were for
the DeBakey — but it’s got some of the same defects as the
DeBakey as far as construction,” says Oyer.
Though questions remain about the Jarvik spinner pump, Robbins is optimistic.
“The Jarvik is now being tested at two sites and the hope is that
in the first quarter of 2002 the FDA will allow a few more hospitals to
put those pumps in,” says Robbins. “We’re hoping we
will be among those who test it next.”
So, despite the allure of a manmade heart and the potential that xenotransplantation
might hold, for now Stanford’s cardiothoracic surgeons are most
confident of LVADs, says Robbins. And when it comes to LVADs, Robbins’
hopes are high.
“What I’m most excited about is the potential of these devices
to support hearts long term, not only as a bridge to transplant but as
an alternative to transplant,” Robbins says.
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