Artificial Heart Pioneer
O.H. Frazier, the Chief of Cardiopulmonary Transplantation at the Texas Heart Institute, stands in the vanguard of researchers testing various partial and total artificial hearts. Their work could help save the lives of hundreds of thousands of people who die every year from coronary heart disease. In this interview, Frazier looks back at the landmark developments in the field as well as discusses the latest innovations.
The need for artificial hearts
NOVA: Will the heart be the first organ that we succeed in replacing?
O. H. Frazier: As far as an internal organ that we can replace, the heart certainly seems to be the organ that will be first. Some research is ongoing with both livers and lungs, but that technology is very early in development. The heart is still a complicated organ to replace (much more than a simple pump) but the technology is better developed. The heart has many properties, including hormonal properties, that we never appreciated when we first started doing this research. In the near future, I think that the heart will be the only organ that will be replaced as a totally artificial or man-made substitute for an internal human organ.
why is it important to develop artificial hearts?
It's important from a lot of standpoints. Too many patients die prematurely. Today, if an active working person in his or her 70s dies from a heart attack, that death is premature. The main cause of premature death in the U.S. and the world is heart disease. Even though we smoke less, eat more healthful foods, and exercise, the incidence of heart disease has not decreased. If anything, it seems to be increasing. In addition, heart disease is a very common cause of death in women as well as men—in fact, heart disease causes death in more women under the age of 60 than breast cancer does—and it also plagues children and young adults.
Heart transplantation is not enough?
Heart transplants were a remarkable advance. I have the dubious honor of probably doing more than anyone, because I'm the only one at our center who does transplant operations. I've done over 700 heart transplants, but I have very mixed feelings about it. Heart transplantation is a wonderful technology, and it helps patients, but it's a rather temporary solution. All of us in the field have been rather discouraged by the limitations of long-term survival, particularly in our young patients.
It's especially hard when we do a transplant in a young child. With a successful heart transplant, a young child (2-3 years old) grows to be 13 or 14, and then may die or require a second transplant. The parents are always grateful, but the situation is really difficult.
It's the same for the young adults. I have patients 25 or 30 years old. They appreciate living another eight to ten years. But they want more, and we want more. Probably the most emotionally satisfying patients we do heart transplants for are those in their 60s, because they are more satisfied with the additional time, which is enough to get them their three score and ten.
Aren't there only about 2,000 hearts available for transplant every year?
Yes, and that number has gone down instead of up. We have fewer homicides, fewer automobile accidents. The helmet laws have made a significant difference in the number of motorcycle fatalities. In the 1980s, hardly a week went by without our seeing a donor who had been killed on a motorcycle. We haven't seen that in years. This is good, actually. After all, it's rather disquieting to have to depend on the misfortune of others for these patients to benefit. In addition, many of the donors we do have are older and more compromised than in previous years.
Also, the cost of heart transplantation is enormous, and there's no way of lessening the cost. A heart transplant requires a team of people in the operating room and a large team of people to take care of these patients after their transplant. For all of these reasons, it's very important that research into artificial hearts continues.
Advent of artificial heart technology
What are your thoughts on the Jarvik-7 artificial heart?
The Jarvik-7, which was designed for long-term use, was an outgrowth of our experience in temporary total artificial hearts as bridges to transplant. Early on [in 1969, 1978, and 1981], we implanted two total artificial hearts and an LVAD [LVADs are left ventricular assist devices—partial artificial hearts that take over pumping blood for the left ventricle] as bridges to transplant. The Jarvik-7 was introduced before it became apparent that the immunosuppressive drug cyclosporine would make transplants feasible again and, importantly, allow bridges to transplant to be successful.
Most of us doing research in the field of artificial hearts were not optimistic about the use of the Jarvik-7 heart as permanent therapy. The calf experiments with the Jarvik-7 showed limited survival. There were frequent problems with infections, with durability, and with strokes or blood clots. So we were a bit skeptical of the outcome. I think there were even some public statements made to that effect by both Dr. [Michael] DeBakey and Dr. [Denton] Cooley at the time this trial began.
"When I was in medical school, the head of our research team ... told me in 1965 that by 1980 there would be 100,000 Americans with a total artificial heart. Of course, there weren't."
But the remarkable thing about that trial was really how well the patients did. All of the patients were dying, and the pump lasted far longer and had far fewer problems than we had anticipated. Of course, all those patients had a lot of spirit and courage as well. We were encouraged by that, because the device was loud and bulky and actually rather traumatic with its forceful pumping. We thought that these problems might be difficult for the patients to accept, but they seemed to accept them very well.
So a lot was learned from the Jarvik-7?
Yes. I think all of us in the field were stunned because the heart worked so well. I saw those patients, and it was absolutely remarkable that they lived as long as they did. One survived about 600 days. I don't think any of the LVADs have lasted much longer. That showed the durability of the human body and the human spirit.
Yet after Jarvik-7, didn't many researchers in the field begin focusing strictly on developing LVADs?
That's right. Historically, we thought the artificial heart would be the answer. When I was in medical school, the head of our research team was one of the most experienced people in the field. He told me in 1965 that by 1980 there would be 100,000 Americans with a total artificial heart. Of course, there weren't. As the difficulties with the total artificial heart became more apparent, we reverted to the use of the LVAD for a lot of reasons, one of which was that it was simpler. We could time the pumping of the LVAD by using the action of the native heart. And by leaving the native heart in place, we didn't have to deal with the space confinements that trying to replace the whole heart gave us.
A real breakthrough in developing LVADs came in 1988 with Richard Wampler's axial-flow pump [a tiny, continuous-flow pump that allows weakened hearts to recover]. Did that pave the way for the new continuous-flow LVADs like the Jarvik-2000 and the DeBakey VAD?
Yes, it really opened up this field. Wampler designed it for use as a temporary pump: a very small, continuous-flow pump that would take the blood out of the heart when the heart failed after a sudden heart attack or right after heart surgery, and pump for a few days to allow the heart to rest.
Our first use of the Hemopump in April 1988 was very dramatic because it showed us that patients could live without a pulse. I had one little boy who lived for about three days without a pulse at all. He was very small, and this tiny pump could take over his entire circulation. He woke up, he ate popsicles, and he did very well for a period of time until his heart had recovered enough to start beating again.
With the Hemopump, we also learned that we could have a very high rate of flow and turbulence in the bloodstream without destroying the blood cells, which was a very important finding. That stimulated others to develop continuous-flow pumps.
What are the advantages of continuous rather than pulsatile (pulse-like) flow?
With continuous flow, there isn't a pulse. Without a pulse, it is not necessary to have volume compensation for the heart. If volume compensation isn't needed, then we don't have to penetrate the skin. If we don't have to penetrate the skin, then we can do away with what I think is the most important problem with long-term devices being used now—infection.
So, continuous flow has many advantages, although it wasn't widely considered until recently because we didn't know whether patients could live without a pulse. Maybe complications would result from pulseless flow. Maybe nature intended for us to have a pulse. How do you feed the pump that pumps the blood and nutrients to the rest of the body? The only way to do that is to give the heart a rest. So, we have a pulse to allow the heart to get its rest and renewed energy. It's a remarkable organ in that regard.
NeXT-generation Artificial Hearts
Do you think the AbioCor total artificial heart [which is slated to begin human trials in the year 2000] is ready for use in human patients?
We're very anxious to use this technology because we will be able to help patients who aren't being helped now. I think we've validated this concept biologically more than adequately. We have studied more than 100 animals with the AbioCor heart, some for more than 100 days, and the pump has worked very well. If it lasts that long in animals, it will work in humans. Reliability testing and further wear testing are ongoing.
"To have all of these varying technologies available off the shelf is our goal. I'm not sure if it will take two years or 20 years."
What are the specific advantages of the AbioCor heart?
What we need is a solution for heart failure that will allow patients to leave the hospital, go back to what they were doing before, and lead meaningful lives. The HeartMate [an LVAD that has been implanted in over 1,500 patients to date] does this to some degree now. Some of our LVAD patients have been able to return to work. But the device is large and loud, and it is powered from outside the body, so it needs to be improved upon.
The AbioCor artificial heart is small, and it was designed for the human heart. The first artificial hearts were designed more for the calf, and the first patients who received those devices were large people. Barney Clark, for instance, was a huge man. He weighed more than 300 pounds, and he was well over 6'4" tall. But the AbioCor pump is designed for the average-sized adult. It's still too big for small adults, but it will fit in most of the U.S. adult population.
Another advantage is that the AbioCor pumps alternately right to left. So it doesn't pump both to the lungs and the body at the same time, like the normal heart, but it pumps side to side. This is an important advantage, because the bulk of the volume compensation that a pulsatile pump needs can be adjusted by using alternating ventricles. So when the left side is pumping, the right side is a volume chamber, and vice versa.
Why is that important?
Well, the right heart and the left heart don't pump the same amount of blood; the left heart pumps more. So there has to be some way of compensating for that variance between the two sides of the heart and the amount of blood pumped. This has been done in a very ingenious way by the engineers who developed the AbioCor heart—a really outstanding engineering accomplishment. They designed a small compensation chamber, which acts in a way to allow the right side of the heart to sense whether it needs to pump more blood or less blood. It automatically adjusts internally according to changes within this little chamber.
It also has a beautiful advantage that I think will make it much less thrombogenic (that is, it will have a very low problem with blood clots or strokes). As in normal human circulation, the blood never stops in this pump. Whenever blood stops, it has a tendency to form clots, and patients need aggressive thinning of the blood. But in the AbioCor, the blood is always moving, either on the right or left side. So, I think that patients will not need as much blood thinning medication with this device, and the incidence of strokes will be lower.
Which patients do you think the AbioCor will benefit most?
The bulk of patients who die within a few days after a heart attack or after open-heart surgery could benefit from these pumps, because they need both ventricles. Artificial hearts are like transplants except they can't be rejected, and they can also be produced in unlimited quantities.
And the AbioCor will be totally enclosed within the body?
Yes. The technology to transmit energy across the skin—that is, without going through the skin—has been available for years. Remember the high school experiment in which you lit an electrical bulb by bringing an electrical field close to the bulb? It's the same principle. A small coil inside the body can be supplied with energy from a small coil on the outside of the body during day-to-day activities. The pump will also have a small internal battery that will supply energy for short periods of time when power needs to be completely internal, like when a patient is taking a shower.
And it's totally quiet. Because of that, I think patients will be able to go back to work easily. Patients with these hearts will look like anyone else—with no tubes or wires to be seen. These patients will be able to work and live in much the same way as a normal person does.
Will we still need LVADs and other heart-assist devices?
I think it's important for surgeons to have a variety of options, because patients have so many variables, beginning with their size and including things as complicated as the amount of resistance within the lungs and whether the patient needs a total heart or a partial heart. There are many different causes of heart failure, and a technology is needed that best addresses that cause. For example, if you thInk the patient's heart wIll recover with a few months of rest, then a small pump that can be put in with very few complications would be best. You don't want to take the whole heart out and put in an artificial heart if all the patient needs is a small temporary pump.
When we first started using the HeartMate in 1986, we used it in very few patients. Last year, more than 500 patients in the United States who would have died had this pump implanted. But the need is still much greater than that, because the number of patients dying prematurely of heart disease is far in excess of what we should accept.
I think that all of the very different technologies we have discussed will play a big role in the treatment of heart disease. To have all of these varying technologies available off the shelf is our goal. I'm not sure if it will take two years or 20 years, but I think it will be achieved.