Hope for Hearts

Most of us aren’t mindful of the constant flow of blood through our bodies, but 20-year-old Maria Amezquita can hardly miss hers.

She can see her blood through the windows of the two plastic and metal pumps embedded in her chest. Valves click. Lights blink on a big, beeping console that sends rhythmic pulses of air down tubes to make the pumps push, then relax.

Amezquita, 20, is waiting at UCLA for a heart to replace her own. It’s no picnic, being tethered to that 450-pound driver while at home her infant grows older without her. But the hardware is keeping her alive so she’ll be around when that donor heart shows up.

Nearby, 19-year-old John Aguilar is waiting too--but right now he’s ambling the hallways, wheeling a small, portable driver that both patients have and use when they want to be more mobile.

Both are suffering from end-stage heart failure--they have hearts, in other words, that can no longer pump powerfully enough to keep their organs alive. They would be dead had not surgeons fitted the metal-and-plastic pumps onto the major arteries and veins that feed the 60,000 miles of vessels in their bodies. Blood flows first into their flesh-and-blood hearts, which do what pumping they can. Then it moves along to the pumps, where it’s sent with more force on its way.

This isn’t a permanent solution. You can’t send someone home with a pump sticking out of his or her body and with a bulky console to which he or she is forever tied. It’s a temporary, lifesaving measure until that heart comes in.

For many others in need, though, a heart never will come in. The shortage of organs for transplant is that severe. Each year, 2,000 to 2,400 hearts are available for transplant. Each year, at least 50,000 people in the United States need new hearts. Now medicine may be in a position to save them. After 40 years of experimentation; after past dashed hopes and years of experience managing temporary, artificial pumps in transplant-bound people like Amezquita, inventors have honed their technology. The AbioCor total artificial heart, so recently in the news with its first few human trials, isn’t the half of it. Scientists have created a smorgasbord of new blood-pumping devices, some that might help many more people than the AbioCor. The new pumps are good enough, experts feel, to be permanently implanted into people who will never, ever get a heart transplant.

“The future is very bright,” says Dr. Michael De Bakey, director of the De Bakey Heart Center in Houston, a pioneer in this and many other fields of heart research. “I’m thankful I’ve lived long enough to see it come to pass.”

The new devices run the gamut: everything from the AbioCor heart to intermediate-sized “assist devices” (called things like “HeartMate” and “LionHeart”) all the way to simple, battery-sized gadgets that look more like rotating screws than the flesh-and-blood pump that we’re born with.

The idea, surgeons say, is not to come up with one solution but an array of them, so that each patient’s needs can be met.

“What we have to have is a spectrum of devices and not get into a mind-set where we use one device for all applications,” says Dr. Walter Pae, professor of surgery at Pennsylvania State University’s college of medicine. “I mean that would be as silly as thinking that one suit of clothes or one of your dresses is going to suit all occasions.”

Some of the pumps are fully enclosed in the body--controls and all--so that nothing sticks out. Others, although physically linked to the outside world, have controls and batteries so slimmed-down they can be worn on a belt round the waist, allowing people to live fairly normal lives.

And while some of the gadgets are still only in trials, others have been saving people’s lives for years. But they’ve not yet made a big dent in the number of people saved. That’s because they’ve only been FDA-approved, up till now, to be implanted in very sick people on the transplant waiting list.

Keep one person alive long enough for a heart, and “you’re just going to displace someone else,” says Dr. Eric Rose, chairman of the department of surgery at Columbia University. “You’re basically playing a game of three-card monte with the donors.”

But this temporary implant experience, says Rose, has done something important--given doctors and inventors across the country a wealth of experience with managing such devices under less-challenging, short-term situations. It led them closer and closer to a permanent solution and to an important clinical trial known as REMATCH.

In a matter of weeks, results of that large trial, conducted by Rose and others around the country, will be released--a trial of people permanently implanted with an assist device that helps the left side of the heart pump blood around the body. Those who got the device were compared with another identical group receiving the best medical care available for end-stage heart failure.

If REMATCH shows that people with the assist device have a significantly better survival rate over two years, with a decent quality of life, heart experts say it’s likely that FDA approval for permanent use of this particular device will follow. Similar approval for other devices would probably come after.

That, combined with the fact that the devices are becoming more sophisticated, will change the nature of the artificial heart and ventricular assist device debate.

“The question used to be: ‘Can we build the technology?”’ says Dr. Mehmet Oz, director of the cardiovascular institute at the Columbia Presbyterian Medical Center. “The question now becomes: ‘Will we pay for the technology?”’

Heart-Lung Machine Invented in the 1950s

The roots of that technology stretch at least back to the ‘50s when the heart-lung machine was invented. Up till then, heart surgeons had to work quickly, sometimes cooling patients’ bodies to slow down their metabolism and buy extra time, says Dr. Jaime Moriguchi, medical director of the mechanical circulatory supports team at UCLA Medical Center.

This new machine, however, could stand in for both heart and lung--sucking oxygen-depleted blood from the major veins, replenishing it with oxygen and then dumping it back in to the aorta.

“It was a big advance; it made surgery a lot more feasible and gave surgeons time to repair very complex congenital abnormalities,” says Moriguchi.

The heart-lung machine could only be used for a short time--but it gave doctors dreams of something grander.

“My feeling along with others in that pioneering period was if we could do it for a few hours then it must be possible to do it for a few days or weeks,” says De Bakey. He and others started working on such devices, and lobbied for a federally funded research program.

Funding began in 1964 and has continued to this day, with dollar amounts and focus that have shifted through the years. One early goal--in retrospect hugely overly optimistic--was to get a fully enclosed artificial heart into a patient by 1970.

For a while, scientists tried to design a nuclear-powered heart, but this was eventually abandoned out of concern for possible hazard.

And, as the years went by, the National Institutes of Health shifted its funding effort toward assist devices that wouldn’t replace the whole heart but would help it do its pumping job. In 1988, in fact, the NIH came within a whisker of withdrawing all funding for a total heart program--but was compelled by political pressure to keep the money flowing. Both efforts chugged on in parallel.

Many devices were developed during this long effort--and along the road a few mechanical hearts were implanted into people. One, in a murky-sounding episode in 1969, was sneaked out of De Bakey’s lab and implanted, without approval, into a man waiting for a transplant. The man lived on the device for 64 hours, but died soon after getting the transplant.

Then came the 1980s--and a media frenzy following the 1982 implantation of the famous Jarvik-7 heart into retired dentist Barney Clark and into four other people over the next few years. Clark lived 112 days; another patient, William Schroeder, lived fully 620. But he lived those days leashed to a noisy console getting sicker and sicker from rampant infection, strokes and multiple organ failure.

Clearly, an artificial heart was not ready for prime time (although a version of the Jarvik-7 heart, called CardioWest, is still being successfully used as a bridge-to-transplant device at the University of Arizona). The experience lodged a distaste in the public mind as strong as the giddy enthusiasm it replaced.

“From my own personal experience, 10 years ago, most of my patients would not think of having an artificial heart--they would rather die,” says Oz. “It became the epitome of the evil science could accomplish.”

It cast a pall too on the effort to develop the devices. But then came the blooming of the heart transplant era--and a growing need. Transplant operations were increasing. The supply of organs wasn’t.

“People were getting to the point where they would get really, really sick and in many cases would die--or would go into the heart transplant so sick that they wouldn’t have enough reserves in their bodies to survive the operation itself,” says Dr. Daniel Marelli, assistant professor of surgery at UCLA Medical Center. Marelli and Moriguchi, with Dr. Hillel Laks, are collaborators on UCLA’s assist-device and AbioCor artificial heart programs.

From the start of the ‘90s, assist devices were used more and more to keep such patients alive while they waited--and scientists pushed on with their quest for a long-term solution.

The Heart Does a Difficult Job

The challenges scientists faced in even building assist devices were huge. Our hearts, after all, push 5 to 10 liters of blood a minute over high pressure, for years and years without resting. They pump faster when we’re trudging up the stairs; pump slower when we’re lounging on the couch. They pump gently enough so as not to damage the blood cells. But always, they keep blood on the move. Blood that isn’t moving tends to clot--and clots, if they get to the brain, can causes stroke.

The materials used in the artificial devices are a clotting problem too. They’re not “smart,” like the lining of our hearts and arteries and veins, which actively discourage clot formation.

And then there is the risk of infection. If a device isn’t totally enclosed--if there are any tubes or wires threading into the body from the outside world--that’s an entryway for germs. And germs grow more easily if the tissue is inflamed or injured; both are quite likely if the immune system’s reacting to a foreign body and that foreign body’s moving at all.

Finally, a device, no matter how nifty, is of little use unless lightweight enough and small enough to be housed in the body it was intended for--and no good for long-term use if it doesn’t allow the wearer a relatively normal life.

As the scientists looked for solutions, their philosophies diverged and so did the roads they traveled.

Some decided it was important to totally enclose a device, supplying it with power by transmitting energy across the skin. That way, you lower your risk of infection; it also means a patient can live a more normal life.

“Just think about the downsides of things coming out of your body; things like swimming, taking a shower and moving about in an unrestricted fashion are a little difficult,” says Pae, who heads a team studying a totally enclosed assist device, the Arrow LionHeart developed at Penn State and Arrow International Inc. (Pennsylvania State University has also developed an artificial heart but it hasn’t yet been tested on people.)

Patients Pae has known who finally get to take a shower “say it is the most wonderful thing.... It’s little things like that.”

The Lionheart, at the moment only in clinical trials, has been implanted into about a score of people so far.

But there are challenges in totally enclosing a device. The Lionheart needs a chamber inside the body where the air that pumps the blood can be shunted while the pump is filling up again: This chamber has to be periodically drained of fluid.

And while the AbioCor heart--which is also totally enclosed--doesn’t have that problem, there is still the matter of hardware. Totally implanting means you have to load more components in the body and be surer of their reliability.

Additionally, should anything go wrong, the patient faces more invasive surgery.

For all these reasons, other research teams have opted to build devices that, while physically linked to the outside, have power sources and controls slimmed down enough to be worn on a belt. The Novacor LVAS, from Canada’s WorldHeart Corp., is one of these; another is the HeartMate VE, an electrically powered assist device from Thoratec Corp. in Pleasanton, Calif. (The HeartMate was the device used in the REMATCH trial.)

Although Thoratec is now working on totally enclosed devices, “we’re slow to conclude that’s a panacea,” says Keith Grossman, the company’s chief executive.

Scientists have also come up with different answers to the blood-clotting problem. The HeartMate, for instance, has a gently textured interior that encourages a layer of proteins and cells to develop. That layer discourages the development of clots that break off and travel to the brain.

Scientists who designed the new AbioCor total artificial heart took a different approach. They built an interior so smooth and streamlined that clots don’t tend to form.

“You can’t have a lot of steps and bumps because if you do then the blood will deposit,” says Robert Kung, chief scientific officer at Abiomed Inc. of Danvers, Mass.

Scientists also debate whether the blood must be pumped in rhythmic pulses if a device is to be more than just temporary. It makes some sense to assume so--after all, that’s how our own heart is built and what our various organs are adapted to dealing with.

But it may not turn out to be the case. Years ago, De Bakey--who had already shifted his focus away from developing a total heart--transplanted a heart into a NASA scientist. That led to a collaboration with NASA, and ultimately to the development of a device akin to a gizmo used on the space shuttle. It’s a tiny, rotary pump that pulls blood through the body at a steady, continuous rate.

Such devices--the MicroMed DeBakey VAD plus two others called the Jarvik 2000 and the HeartMate 2--can be much smaller than the rhythmic devices, allowing them to be fit into patients with a much wider range of body sizes. Many people are too small for devices like the LionHeart, HeartMate and AbioCor.

They also are the epitome of simplicity, with just one, single moving part--and thus far fewer parts that can fail.

That is the way of the future, says Dr. Robert Jarvik, inventor of the Jarvik-7 and now the Jarvik 2000, and president of Jarvik Heart Inc. in New York. To Jarvik’s way of thinking, a total artificial heart is “an obsolete approach.”

“There is this idea that if one can make something very complicated work that it’s some sort of engineering masterpiece,” he says. “We’ve become convinced that something highly miniaturized and simple is better.”

Others are far more enthusiastic about the AbioCor heart, which has been functioning flawlessly so far in 59-year-old Franklin, Ky., retiree Robert Tools and two others.

These first three AbioCor implants have been accompanied with restraint and respect for the privacy of family and patient that were totally lacking in the 1980s Jarvik-7 experience, where upbeat, blow-by-blow accounts of the patients’ lives and progress were disclosed and reported by the media.

“They’ve been very careful not to turn it into a media circus--not to make exuberant claims about how well the patient is doing and to emphasize again and again how sick he was and how experimental the implantation of this device is,” says sociologist of medicine Renee Fox, professor emeritus of the University of Pennsylvania, and author of a book, “Spare Parts,” which chronicled the Barney Clark experience.

Finding the Best Device for the Individual Patient

Cutting out a heart and putting in a new one is a drastic and irreversible thing to do. (“If it breaks, the ballgame’s over,” says Moriguchi.)

Still, a total heart will be the treatment of choice for many patients, says Dr. Bud Frazier, surgeon at the Texas Heart Institute in Houston. It’s not a matter, Frazier says, of devices duking it out until one becomes top dog: It’s a matter of figuring out which patient is best served by what.

To Frazier’s and other experts’ mind, the device pie can be divided into three, rough pieces:

People whose hearts are damaged on both sides will need a total artificial heart.

People whose hearts are pretty much shot on the left side only will need devices like the HeartMate or Novacor that can take up the slack for most or all of the left’s pumping action. (Most hearts fail on the left.)

Finally, those whose hearts are failing on the left but can still pump some blood could get by nicely with the futuristic battery-sized devices like the Jarvik 2000 or De Bakey VAD.

In fact, Frazier says, it’s possible, down the road, that people could get treated with these smallest-of-small devices earlier on in the progression of their disease. Before they get really, really sick.

Scientists and doctors who work with artificial hearts and assist devices say the technology’s still far from perfect. They need more powerful, smaller batteries; better ways to deal with blood clots and infection; more assurance that these devices can pump away in the human body for years without malfunctioning.

But today, they believe, the technology is good enough to start saving more people’s lives. Soon, they predict, people like Amezquita and Aguilar, new donor hearts in place, back dandling toddlers, kicking balls, getting groceries--will be rarer by far than those walking around with life-giving metal and plastic in their chests.

At a cost. Nobody knows exactly how many people can ultimately be helped by these devices each year but it is likely to be tens--maybe hundreds--of thousands. And nobody knows how much the devices will cost--though with hardware and surgery factored in, each implant is likely to be as expensive as a heart transplant.

Which leads to the next, tricky question: Can society afford it?

“This may be the first time in history where we can actually do it--but we may not want to pay for it,” says Oz. “This discussion has to be a public one. If we’re not going to pay for artificial hearts just to keep people alive, we should as a country decide that we’re not going to pay for it. We shouldn’t let Medicare and private insurers decide whether or not we use this technology.”

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Helping Devices

Hearts may have varying levels of failure. Scientists have developed a range of devices that can assist--or replace--the function of the heart.

The Heart

The right side of the heart pumps blood to the lungs to collect oxygen. The blood then returns to the heart. The left side then pumps this oxygen-rich blood to the rest of the body. Both sides of the heart can fail, but failure of the left side is more common.

Total Artificial Heart

The AbioCor artificial heart, currently in human trials, is the only total replacement for the heart. So far, the AbioCor has been implanted into Robert Tools and two others. (UCLA is one of five sites involved in early AbioCor trials.) Its likely future use is in people with heart failure in both sides.

Left Ventricular Assist Devices

Devices like the HeartMate VE, the Novacor LVAS and the Arrow LionHeart do the job of the left side of the heart. The heart is not removed when the devices are implanted.

Axial Flow Pumps

Devices such as the De Bakey VAD, Jarvik 2000 and HeartMate II pump blood without supplying a pulse. Because they’re tiny, they can fit smaller bodies. Designed to aid, not replace, they’re for hearts whose left side, though it works, needs help. Right aids are possible too.