Artificial Mini-Hearts Developed
Medicine's holy grail might be whirring away at a lab outside San Francisco, Calif. where, in rows of containers, tiny rotary pumps relentlessly speed a clear liquid solution through a tube. Or maybe it can be found in an industrial park in Boston, where grapefruit-sized titanium and plastic pumps lined up in steel tanks beat with a precision that would satisfy a Swiss watchmaker. Or, perhaps, at WorldHeart Corp.'s Ottawa headquarters, where an even smaller pump pushes a clear fluid through a polymer chamber at the rate of up to 10 litres a minute. In more than half a dozen North American facilities, researchers are engaged in what promises to be one of the most lucrative and laudable competitions in modern medicine - the invention of an artificial heart capable of extending the lives of hundreds of thousands of people indefinitely.
The race is on, and a Canadian company is a serious contender in opening up a new sector of cardiac medicine that carries the prospect of making whoever gets there first very, very rich. WorldHeart intends to put its HeartSaverVAD, a hand-sized pump, through its paces in human trials by the end of this year. Government approval to market the wonder machine could follow, it hopes, by the end of 2004. The HeartSaver has already been tested on cows, says a confident Rod Bryden, WorldHeart's president and chief executive officer, "and we haven't had any failures yet."
Such optimism is not new in the artificial heart business. As far back as 1969, when Dr. Denton Cooley implanted the first complete mechanical heart in a human in Houston, Tex., some predicted the breakthrough technology was five or 10 years away. That device kept patient Haskell Karp alive for 64 hours until he received a heart transplant - but he died just 36 hours later. It was 13 years before the next headline-grabbing milestone, the famous Jarvik-7 pump installed in Seattle, Wash., in the chest of Barney Clark, who became the poster boy for technological hubris. He survived 112 days, but it was an excruciating time: he suffered a series of strokes before finally succumbing. Nineteen years elapsed before the next big step forward, if that's the right term. Last July, in Louisville, Ky., 59-year-old Robert Tools became the first recipient of a full artificial heart that allowed the patient enough mobility to leave the hospital, the AbioCor heart by Abiomed Inc. of Danvers, Mass. Tools lived for 151 days.
The AbioCor model may mark the end of the road for the dream of replacing the entire heart with a man-made device in the vast majority of cases. Instead, there is a growing consensus that those seminal operations, which seemed to forecast a brave new race of people with indestructible hearts, have led to a conceptual dead end. "It's an interesting intellectual challenge to try to replace the human pump, but it has limited use," says Doug Loe, a health industry analyst with Yorkton Securities in Toronto. Even Dr. Robert Jarvik has given up on the eponymous machine that made him a household name. "Replacement of the heart," he told Maclean's, "is pretty much an obsolete approach."
For one thing, it demands a level of reliability never approached by man-made machines. The human heart expands and contracts roughly 100,000 times a day, pumping about 8,000 litres of blood. Over a lifetime of 70 years, the heart beats more than 2.5 billion times, with no pit stops for lube jobs or repairs. Moreover, it's rarely necessary to replace the whole organ. Most of the heavy lifting is done by the left ventricle, the chamber that pumps re-oxygenated blood to the far reaches of the body. The right ventricle has the comparatively easy chore of pushing spent blood to the nearby lungs. That means that in about 85 per cent of heart-failure patients, only the left ventricle is worn out. So, Jarvik and other experts wondered, why try to replace the entire organ?
By the late 1970s, that logic led most artificial heart researchers to refocus their efforts on technologically simpler mini-hearts. Known as VADs - for ventricular assist devices - these little pumps that aid the natural heart are fast turning science fiction into fact. VAD development - mostly for the left ventricle but also adaptable to rare cases in which the right side of the heart has failed - has attracted some of the biggest names in cardiovascular medicine, including Jarvik. Another star is Dr. Michael DeBakey of Houston, who worked on developing a total artificial heart in the 1960s before shifting his attention to VADs. In Ottawa, renowned heart surgeon Wilbert Keon began assembling his VAD team, which eventually became WorldHeart, in 1989. "I've been working on this problem for nearly 50 years," says DeBakey, "and we're finally at the point where we can start thinking of making artificial devices as dependable as heart transplants."
The journey from conception to reality was considerably shorter for Keon. Piggy-backing on the pioneering work of others, the Ottawa surgeon imagined the next step in VAD development and set out to achieve it. In 1989, he lured Dr. Tofy Mussivand north from the Cleveland Clinic to work on a vision - a ventricular assist system that would be totally implantable in the chest cavity. Other VAD development of the era envisioned a fairly bulky mechanical pump housed in the abdomen below the rib cage, connected by tubes to the heart, and with a wire protruding through the skin to an exterior power pack. "When I first explained what we were working on to a U.S. surgeon, he thought I was nuts," recalls Mussivand.
In retrospect, says Mussivand, the real miracle of the HeartSaver's development has been finding the financing. That's where Bryden, a local high-tech entrepreneur and owner of the Ottawa Senators hockey team, came in. Bryden's WorldHeart company, established in 1996, has been able to raise $99.5 million in research financing to bring the HeartSaverVAD, weighing two pounds and small enough to fit inside the chest beside the ailing heart, to the point where it can be tried in human beings. "It's clear that the HeartSaver is about to set a new standard for next-generation VADs," says Chris Sassouni, a research analyst working with eResearch, a Toronto-based market analysis firm, who in November prepared a 221-page report on WorldHeart. In 2001 alone, keen investors injected $21 million into the company.
One big reason the VAD doesn't look like such a wild gamble any more is that modest versions of the pump are already working. Used in human trials for almost two decades, some types of VADs have been approved for use in Canada since 1999 to keep patients with failed hearts going until a human donor is found. That track record gives ample evidence that the next step - using VADs such as HeartSaver not as a stopgap, but as a permanent alternative to heart transplants - is close at hand. WorldHeart bought a major maker of these temporary VADs - a division of Edwards Novacor LLC of Oakland, Calif. - in June, 2000. Its Novacor LVAS pumping system has already been implanted in more than 1,300 patients worldwide - including 10 in Canada.
Two European patients awaiting transplants have lived more than four years on the pump. So reliably have the devices performed that last month, WorldHeart began testing the Novacor unit for long-term use in Canadian patients who are not eligible for heart transplants. Denis Demers, 61, a Montreal cook, became the first of about 30 who will receive the mechanical version during the trial in six Canadian hospitals.
Until now, Matthew Watson, a 21-year-old psychology student at Ottawa's Carleton University, has been typical of people who received VADs in Canada. The point was simply to keep patients with heart problems alive long enough for a human heart to become available for transplant. Diagnosed at 17 with a congestive heart defect (his heart could not pump sufficient blood), he seemed to have little hope until Ottawa surgeon Paul Hendry installed the two-pound mechanical pump in his abdomen last May. Powered by an external battery pack the size of small transistor radio strapped around his waist, the device kept him going until he received his new heart on Jan. 31. Watson says living with the mechanical pump was not as difficult or exotic as some might assume. "I could exercise, go skating, go out with friends," he says. Even, he confirms hesitantly, have a normal sex life. The device does, however, make for some humorous moments. The Novacor model, like other current-generation VADs, emits an audible clicking that speeds up when his heart beats faster. "The first time I noticed it was in the hospital when a cute nurse came into my room," he recalls with a smile. "It started beating louder."
For Watson, current technology is sufficient for his need. But as amazing as they seem, the VADs now in use do nothing to reduce the overall death toll from heart disease. The grim fact is that, until the current Novacor trials, every person whose life has been extended by a VAD was a candidate for a donor heart that might have gone to someone else. And there simply aren't enough hearts to go around. In the U.S., roughly 300,000 people die each year from congestive heart failure and related causes; in Canada, estimates are in the 25,000 to 30,000 range. But only about 2,500 heart transplants are performed in all of North America each year, including about 180 in Canada. So for every Watson saved by a VAD, someone else on the transplant waiting list dies. So far, Bryden says bluntly, "all we're doing is changing the name on the death certificate."
To have a significant impact on one of the leading causes of death, scientists must perfect an artificial pump that works as well as - and for as long as - a transplanted human heart. That's a tall order. Transplant patients on average live about 10 years before needing yet another new heart (which they rarely get). While the natural heart does wear out, no one has yet built a machine to rival its durability. But Mussivand knows it's possible. An early prototype of the HeartSaver has been clicking away in a glass tank down the hall from his office since Oct. 15, 1992. "When we started it up we thought it would work about 80 days," Mussivand says. "Now we don't know when it'll stop."
That doesn't mean Ottawa's HeartSaverVADs, which are about 30 per cent smaller than the Novacor and much quieter, are necessarily good for a decade. Other things can go wrong. The device is powered by a small internal battery which, with present technology, must be replaced every two years. The major source of power, though, is an external pack strapped around the waist. It sends electromagnetic radiation through the skin to enable a receptor to generate the power that runs the pump. Because electromagnetic waves - and not an electrical current - pass through the body, the patient feels nothing.
It's a complex system that generates skepticism along with power. Some critics question whether there is enough room in the chest cavity to contain the unit. Others doubt the practicality of transmitting energy through the skin. In fact, glitches have already set the program back about a year, although Mussivand says they have been solved. As for the pump's size, he says tests on human cadavers show it can easily fit beside the heart. He also points out that, with the HeartSaver, the absence of an opening in the skin avoids the risk of infection, a common problem with other VADs. As well, locating the pump in the chest, rather than in the abdomen, reduces the length of connecting tubes, another source of complications. "We think it's important that the HeartSaver is totally contained in the chest without body openings," Mussivand says.
The reward for the HeartSaver's developers, besides the satisfaction of saving lives, could be phenomenal. The market for temporary VADs is not expected to grow above $200 million a year, its size limited by the fact that the devices are only used to keep alive the relatively few patients lucky enough to be deemed good candidates for transplanted hearts that all too rarely become available. But that same scarcity of the genuine article would drive demand for a permanent artificial pump much higher. Sassouni puts potential annual sales at between $5 billion and $10 billion. "It would make the market for VADs one of the largest in the history of the medical device industry," he says.
With such a prize on the horizon, there are plenty of competitors manoeuvring to claim the biggest slice. Jarvik, for one, is placing his bet on the Jarvik 2000, a rotary-motor pump the size of a C battery. Implanted inside the heart, it would get its power from an external source using an infection-resistant wire through the skin. DeBakey also has a tiny rotary pump, the MicroMed DeBakey VAD, in clinical trials in Europe. These devices would have some advantages over WorldHeart's HeartSaverVAD: they are smaller and mechanically simpler, require less invasive surgery and need less power to operate. They are also cheaper, about $63,000 compared to an estimated $75,000 for the HeartSaver. "It should not be a goal of the field of artificial hearts to create vastly expensive, elaborate rescue devices," argues Jarvik.
But the miniaturization championed by Jarvik, DeBakey and others requires trade-offs. The HeartSaver's valves open and close in time with the natural rhythm of the heart, creating a pulse. All rotary pumps now in clinical trials produce a continuous flow of blood. That means the patient has little to no pulse, a potential problem in that some organs - the brain, liver and kidneys among them - may require a pulse pressure. Many experts also believe the steady beat of life is needed to maintain the elasticity of arteries and veins. It remains unclear whether patients who have used the rotary devices for some months while awaiting a transplant will experience problems later on. "A lot of the hormonal connection and neurological connections between the heart and the rest of the body are dependent on the pulse," notes Dr. Alan Gass, director of transplant cardiology at Mount Sinai Medical Center in New York City. "We don't know yet what the brain and kidneys and liver and muscles are going to do without a pulse."
One response to the continuous-flow versus steady-pulse debate is to hedge your bet. Thoratec Corp., the San Francisco-area market leader in the current generation of VADs, is doing just that. The company is developing a rotary system, the HeartMate III, that would have no wiring through the skin and would function as either a continuous-flow or a pulse-producing pump. "If we assume all the devices work the way they're supposed to," says Thoratec president Keith Grossman, "ours will be a category killer."
But Thoratec's ambitiously versatile device is still a few years away from human trials. For WorldHeart, that key test is only months away. The Ottawa company's most immediate competition comes from Arrow International Inc. of Reading, Pa. Ahead of WorldHeart in development, Arrow's LionHeart left-ventricle support pump pretty much does everything the HeartSaver is supposed to. It's a pulse-generating pump, it's fully contained in the body, and it gets its juice without a wire to an outside power source. The difference is in their placement. While the HeartSaver's flat profile can fit in the chest, the thicker configuration of the LionHeart means it must be implanted in the abdomen. If the two work equally well, there's no question, Bryden contends, that patients will choose the HeartSaver.
So who will win the big prize? Merely figuring out who's closest to human trials isn't necessarily enough to go on. "In the VAD market, you never quite know who's ahead until the end," says Grossman. "You can get to clinical trials first, but if the outcomes are not there, you might find the delay is another six years." Jarvik doesn't like to talk of victors. "The real story," he says, "is inventing a practical device that can be used by almost all hospitals that do cardiac surgery, that allows people to function with very little medical follow-up, that allows them to walk a mile, go to work, and travel without restrictions."
Even the order in which rivals ultimately get government approvals, adds Jarvik, will not necessarily determine success. In fact, Bryden thinks the market is too big to be cornered by any single manufacturer. By the end of the decade, he predicts, patients and their doctors will be able to choose from a variety of heart devices.
Pete Kenyon is waiting for that day. After two heart attacks, the 63-year-old Darien, Conn., reinsurance broker was told in 1998 that he had at most a few months to live. "I was close to pushing up daisies," he says. On Aug. 11, 1998, Kenyon received a new lease on life, with a Novacor pump. "I was able to go back to work, go out to dinner, travel," he says. "I even helped build patio furniture for my yard. The only thing I couldn't do is water sports because if I fell in, the circuits would short." The next step for Kenyon was a heart transplant, which he received on Jan. 2. But he has good reason to stay abreast of WorldHeart's development of the HeartSaver. "They're not there yet in being able to take the place of heart transplants," he says, "but they'll get there." Should his new human heart fail in a few years, as transplants usually do, Kenyon may find himself counting on the next-generation VADs to take him to the end of his life. "It's a miraculous world we're living in," he says. The question is who will make this particular miracle happen first, cheaper and best?
Just a Heartbeat Away
In a few short months, R.J. Brack went from being a swimmer with a bright Olympic dream to a teenager with a very bleak future. In 1999, the then 18-year-old Montrealer was training hard to compete in the Canadian nationals swimming meet when he began having difficulty breathing. "I thought I had pulled a diaphragm muscle," he recalls. But it didn't clear up. Instead, it got worse, and then catastrophe hit. On Feb. 4, 2000, he went into cardiac arrest and almost lost his life. "I don't remember anything for the next six weeks," he says. "They had me on morphine the whole time."
When he came to his senses in March, he discovered what a close call he'd had. Attached to his waist was a battery pack with an electrical wire leading through his skin into his abdomen. That provided the power, he learned, for a Novacor left ventricular assist system (LVAS) that his parents had agreed to have implanted in his body. "It was either this or I'm dead," he said. Then Brack, who prefers R.J. to his given names Russel James, began to dream again. Being young and otherwise fit, of average build at 5-feet-10 and 160 lbs., and having the common blood type O, Brack was a prime candidate for a transplant. He received a new heart on May 31 and was back in the pool within six months.
"What can I say? It saved my life," he says of the mechanical device a little larger than a grapefruit that briefly took over the major function of his heart - pumping blood - two years ago. A lifesaver, yes, but not the life he wanted. "I had energy, but the thing ticked constantly," he says. "And worse, I couldn't go swimming." No such problem with the new heart, however, and just over a year after the operation, in August, 2001, Brack was taking part in the World Transplant Games in Kobe, Japan. Competing against other organ recipients from around the globe, Brack set four world records and picked up five gold medals.
Now, he wants to set a record of another kind. "I'm one of the youngest people to receive a heart transplant and I want to become one of the oldest living transplant patients," he says. The record now is 24 years. By that time, Brack figures, he may be in a better position to beat the odds by being among the first to have his heart rebuilt through technology derived from stem cell research. Failing that, he could benefit from advances in artificial heart technology. The prospect of living with a mechanical heart - at least, one that's better that the ticker he had - doesn't faze Brack. "People have artificial arms and legs," he says. "It's no different."
Pumping New Life into the Artificial Heart
Ottawa-based WorldHeart plans to start human trials of its revolutionary HeartSaverVAD by the end of this year. The system sets new standards by placing its small, thin pump device next to the heart, rather than in the abdomen, and eliminating the need for wiring to pass through the skin to provide power.
Standing in for the Ailing Heart
1953, Philadelphia, Pa.: Dr. John Gibbon makes first use of heart-lung machine to temporarily replace heart function in patient.
1958, Stockholm: Arne Larsson, a Swedish heart patient, receives the world's first implanted pacemaker. Larsson gets a total of 26 pacemakers before dying last December at 86.
1967, Cape Town, South Africa: Dr. Christiaan Barnard performs first heart transplant. Patient Louis Washkansky, a 52-year-old grocer, lives 18 days.
1969, Houston, Tex.: Dr. Denton Cooley implants first artificial heart. It sustains patient Haskell Karp, 47, until he receives a transplant 64 hours later. He lives just a day and a half more.
1982, Seattle, Wash.: Robert Jarvik's artificial heart is installed in patient Barney Clark, 61. The Jarvik-7 allows Clark some mobility, but he dies after 112 days. Jarvik subsequently abandons the quest to perfect a full artificial heart.
1988, Washington: The U.S. Food and Drug Administration approves the Novacor and HeartMate left ventricular assist devices - in essence replacements only for the main pumping quarter of the heart - for commercial use.
2001, Louisville, Ky.: The totally implantable AbioCor artificial heart, which allows patient to leave a hospital setting, is used in first human trial. Patient Robert Tools, 59, lives 151 days.
January 2002, Stanford, Calif.: The longest surviving heart transplant recipient, operated on at the age of 14 at the Stanford University Medical Center, passes the 25-year mark with his new organ.
Maclean's March 25, 2002
In response to the blood flow into the natural heart, the HeartSaver ventricular assist device varies the rate of its beat to send enough blood into the body to meet its changing requirements.
Anchored to the rib cage right next to the heart, the HeartSaverVAD takes over the function of a damaged left ventricle, the main pumping chamber.
A removable coil attached to the external battery pack passes power across skin and tissue to an internal lead, which takes the power to the device and keeps the internal battery charged.
The internal battery holds enough power to keep the pump working for two hours without external power.
The external batteries can operate for up to eight hours without recharging.