Robert Jarvik, MD is widely known as the inventor of the first successful permanent artificial heart, the Jarvik 7. In 1982, the first implantation of the Jarvik 7 in patient Barney Clark caught the attention of media around the world. The extraordinary openness of this medical experiment, facilitated by the University of Utah, fueled heated public debate on all aspects of medical research. But as doctors learned how to achieve excellent clinical outcomes in subsequent patients with the Jarvik 7, the press and public largely lost interest in the subject. As a result, outdated and erroneous accounts have made their way into mainstream discussions of the Jarvik 7 time and time again. I sat down with Dr. Jarvik to discuss common mistakes and misimpressions about the first permanent artificial heart, a device that is still used today and has the highest success rate of any mechanical heart or assist device in the world.
In essence, two types of artificial hearts exist: the total artificial heart — which is implanted after the natural heart is removed — and the ventricular assist device — which is implanted to assist the natural heart, leaving the patient's own heart in place and still functioning.
"Removing a person's heart is one of the most dramatic surgical procedures one can imagine," says Dr. Jarvik, who began developing a tiny ventricular assist device, the Jarvik 2000, in 1988. "It is no surprise that more public attention is given to replacing a heart than to assisting one. But consider this question: If you had a failing arm or leg, would you rather have the best-possible artificial limb or a device that allowed you to keep your own arm or leg?"
The question is rhetorical. But while ventricular assist devices find wider application in patients than total artificial hearts, experts view the two as complementary treatments. For example, a total artificial heart is required when an assist device will not do, as in cases of biventricular failure when both sides of the natural heart falter.
In the 60s and 70s, mechanical hearts were being developed by the National Institutes of Health (NIH) but were largely unknown to the public. Then in 1967, Christian Bernard performed the first human heart transplant, an event that generated worldwide interest: People were suddenly aware of heart replacement as a way to treat a failing heart. In 1969, Denton Cooley performed the first implantation of a temporary total artificial heart, and the primitive device sustained the patient for almost three days until a donor was found through an urgent appeal in the press. After another decade and a half of NIH-supported research, the Jarvik 7 heart became the first total artificial heart implanted as a permanent replacement for a hopelessly diseased natural heart.
At the University of Utah on December 2, 1982, William DeVries, MD implanted the Jarvik 7 total artificial into Barney Clark, a Seattle dentist who volunteered to undergo the pioneering procedure because he wanted to make a contribution to medical science. Dr. Jarvik recalls that, before the surgery, Dr. Clark told doctors that he didn't expect to live more than a few days with the experimental heart, but he hoped that what the doctors learned might help save the lives of others someday.
Dr. Jarvik, who headed the company that manufactured the Jarvik 7 heart, agreed with University administrators to give no information to the press directly: no press releases and no interviews. Information would flow through the University press office, instead. The stated goal was to adhere to the highest ethical principles and to conduct this important medical research openly, with no effort to influence or restrict the press. Little press was desired or expected. The University held a briefing before the historic surgery, and attendance was moderate.
"The news about Barney Clark stunned the doctors by making headlines around the world", Dr. Jarvik says. "Enormous public interest developed, and hundreds of reporters converged on Salt Lake City to cover the story, and the University began to give them daily briefings, which were completely uncensored. All medically significant events in the post-operative course were reported, successes and setbacks alike."
The briefings were educational and contained much medical information, including explanations of basic physiology, interpretations of laboratory tests and x-rays, and lengthy question-and-answer sessions. All of the complications were fully reported, as well as the effectiveness of the mechanical heart at maintaining Dr. Clark's normal blood flow and sustaining his life.
"The sheer volume of information and the extraordinary degree of transparency created a sort of medical experiment in a fishbowl," Dr. Jarvik says. The University of Utah achieved its research and educational goals, but the press coverage seemed to leave its readers with unreasonable hopes and expectations: Many began to believe that artificial hearts would soon be commonplace and all but solve the problem of heart disease. The intense attention also attracted critics who apparently knew nothing of Dr. Clark's generous intentions and labeled him a "human guinea pig." Later, Dr. Clark's widow attempted to change this misimpression in order to give her husband the humanitarian credit he deserved. But Mrs. Clark received much less press than the critical commentary, and her mission ultimately foundered. Before another case could be conducted, Dr. DeVries, the surgeon, accepted an offer to join the research program at Humana Hospital in Louisville, Kentucky, and took his expertise there.
The next several implantations of the Jarvik 7 heart, conducted by Humana — a national hospital chain — were handled like the first: with the release of extensive medical information and an open press policy. The second Jarvik 7 implant took place in 1985. Bill Schroeder, the patient, did so well initially that when President Ronald Reagan phoned him with get-well wishes a week later, he asked the president why his social security check was late. (It was hand-delivered the next day.) Mr. Schroeder gave optimistic interviews to reporters and even joked that his noisy drive console "sounded like an old fashioned thrashing machine." But only two weeks after surgery, he suffered a serious stroke that left him unable to speak. Mr. Schroeder later moved from the hospital and lived with his wife in a nearby apartment, which had been outfitted with the special equipment he needed, including an air compressor and emergency generator. When traveling, he used a portable, compressed-air power system, which weighed about fifteen pounds. During his time on the Jarvik 7, he visited his hometown in Indiana and rode down Main Street in a parade, attended a basketball game, and went fishing, but in a limited way: He had many medical problems, including other serious strokes and infections. In all, Mr. Schroeder lived 620 days with his heart function restored but handicapped by his complications.
Three other patients received the Jarvik 7 heart for permanent use over the next year — two more in Louisville and one in Sweden. One patient died of bleeding a week following the operation; the others lived 10 months and 14 months. As it turned out, the Swedish patient was a man accused of tax evasion, but after his heart was removed, he was declared legally dead because under Swedish law, a person was dead when his or her heart stopped beating. The charges against him were officially dropped. The day he received the news, the patient was elated: He joked to his doctors that the old saying about nothing being certain but death and taxes isn't true.
After the first five permanent cases, the Jarvik 7 heart became more widely used as a temporary total artificial heart, bridging patients to transplant. The sixth patient lived five years after a donor heart was found, and the seventh patient lived eleven years with his donated heart. Another patient was bridged from the Jarvik 7 heart to a human heart that gave him fourteen more years of normal life. The press was unaware of these successes, or perhaps considered the subject old news, which, Dr. Jarvik says, was "more than fine" with the doctors involved. But as time went on, the press began reporting erroneously that use of the Jarvik 7 heart had halted after the first five. Later this turned into reporting erroneously that the Food and Drug Administration (FDA) had banned its use. Still later, this turned into reporting erroneously that the Jarvik 7 heart was a failed experiment: The press had begun to believe its own errors.
Since 1982, more than 350 patients have used the Jarvik 7 heart, and it remains in use today. The first few patients lived an average of 10 months (when their life expectancy was only days to weeks). Complication rates were high. "That's where the press stopped doing research and checking facts and instead began to publish mistake after mistake after mistake," Dr. Jarvik notes. All aspects of the experience, from the role of public funding of the research, to the ethics of human experimentation, were debated, but often on a foundation of misinformation. Newspaper and magazine articles with outdated and mistaken accounts appeared. Books with numerous errors were published. In the meantime, doctors gained experience with the Jarvik 7 and learned how to manage their patients more effectively and with fewer complications.
"Knowledgeable doctors watched with amazement as glaring errors appeared in print and then were repeated again and again as newspapers and magazines copied earlier stories and each other and didn't take the time to get information from original sources," says Dr. Jarvik. "Very rarely did I receive a phone call to check the facts. For example, the press wrote repeatedly that Dr. Clark died of a stroke. In fact, he never had a stroke at all. The press wrote over and over that the console a patient needed to power the heart was 'as large as a refrigerator.' In fact, the home console is about half that size, but more significantly — the portable power system was only the size of a briefcase."
And there's more, says Dr. Jarvik. "The press also wrote that the Jarvik 7 heart caused a high rate of strokes and infections. The press didn't notice that as more cases were done, these rates plummeted, yet the device was the same. So the device alone was never responsible for the earlier complications. Rather, doctors needed to learn how to manage their patients more effectively: That is the point of such research in the first place."
Perhaps the most glaring error of all is one that pops up from time to time in the diatribes of some self-proclaimed pundits: that the Jarvik 7 heart was a failed experiment. In fact, it has achieved the highest success rate of any type of artificial heart or assist device that has ever been developed. (See details below.) Today, the Jarvik 7 heart is available at about ten medical centers in the United States, Canada, France, and Germany under the name CardioWest total artificial heart. (Ownership has changed hands several times, but the device design remains essentially unchanged.)
In 1986, Dr. Jarvik was Chairman and CEO of Symbion, Inc., a public company that manufactured the Jarvik 7 heart. A venture capital firm that had financed Symbion made a hostile takeover bid. Dr. Jarvik opposed the takeover and filed a complaint with the Securities and Exchange Commission because the venture capital firm had access to confidential information. He did not succeed in stopping it, though, and lost his position as a result. He then founded Jarvik Heart, Inc., and began work in a different direction to create the Jarvik 2000 heart, a ventricular assist device. Production of the Jarvik 7 heart continued without him.
In 1990, after the Jarvik 7 had been used in 198 patients, Symbion stopped production of the device because the company was no longer in compliance with FDA record-keeping and reporting requirements. The press falsely reported that the FDA removed the Jarvik 7 from the market because the device had a high failure rate. In fact, failures of the Jarvik 7 were extremely rare. The implanted Jarvik 7 heart is more reliable and has had fewer mechanical failures than any implanted positive displacement artificial heart (less than 2% diaphragm failure in the 81-patient FDA study). As a comparison, Dr. Jarvik notes that the HeartMate device had a rate of re-operation for repair or replacement of over 75% within two years in a large randomized clinical trial called REMATCH. The Novacor device has a rate of re-operation for replacement or repair of 16% between two and three years, based on review of the records of 1077 patients. Also, almost all Novacor devices experience failure of the main bearing between three and four years and must be replaced with a new device.
Later in 1990, Symbion transferred its rights to the MedForte Research Foundation, which in 1991, formed CardioWest Technologies, Inc., in collaboration with University Medical Center in Tucson, Arizona. The Jarvik 7 heart was then renamed the CardioWest heart, and Symbion closed its doors. The CardioWest heart is identical to the small size Jarvik 7 heart developed for use in women and smaller men in the mid-1980s. The device uses the same blood pump design, the same Medtronic-Hall valves, and the same external power system as used with the original small size Jarvik 7 heart. The only changes are the use of smaller diameter air power tubes entering the body, and an up to date laptop computer replacing the portable Compaq computer originally used.
In 1993, CardioWest Technologies received approval to conduct a clinical investigation of the heart as a bridge to transplant at five U.S. medical centers. The study demonstrated that the Jarvik 7 heart (CardioWest) is safe and effective. When the study was completed in 2003, the company again changed its ownership and name, this time to SynCardia, Inc., its present status.
The FDA study took ten years to complete and involved 95 patients. It showed a 79% success rate for bridge to transplant and excellent overall survival including transplant (70% at one year, 50% at five years, and 45% at eight years). So, in the U.S. study, the Jarvik 7 (CardioWest) has a better rate of bridge-to-transplant success than any other total artificial heart or any ventricular assist device ever developed. The success rate in foreign countries is lower, but still better than other devices. On March 17, 2004, an FDA review panel recommended PreMarket Approval (PMA) of the heart for bridge-to-transplant use. On October 18, 2004, that approval was granted, making the Jarvik 7 the first total artificial heart to receive full FDA approval for any indication for use. "Far from being a failure," says Dr. Jarvik, "the [Jarvik 7] heart is a documented success."
The only other total artificial heart now available for use in a patient is the AbioCor, which was approved by the FDA for investigational use in 15 patients. The AbioCor has been implanted in 14 patients over the three years following the first case. If a PMA study with the AbioCor were conducted at this enrollment rate — assuming about 95 patients as in the Jarvik 7 (CardioWest) clinical trial — the study would take 20 years to complete.
"The Jarvik 7 is inherently more reliable than the AbioCor because of the simplicity of the Jarvik 7 components and because the multi-layer low-stress design of the most critical component — the flexing diaphragm," says Dr. Jarvik. "The Jarvik 7 has been run on the bench for over six years without failures, and one early prototype at the University of Utah was run continuously on the bench for over ten years."
By contrast, the AbioCor is a highly complex device with numerous implanted components subject to failure. In fact, the second implanted AbioCor heart had two malfunctions: the first requiring re-operation to replace the implanted battery, which weakened prematurely; and the second involving a worn diaphragm — one of the critical components of the device — which caused the death of the patient when it failed.
According to Dr. Jarvik, the major advantage of the Jarvik 7 heart is its hemodynamic effectiveness as a rescue device in patients suffering extreme heart failure and serious secondary damage to other organ systems. It provides higher blood flow than the AbioCor heart in actual patient use (about 10L/min for the Jarvik 7 compared to about 7 L/min for the AbioCor). Higher flow is beneficial for recovery of kidney, liver, lung, and gastrointestinal function, all of which are seriously compromised in near-death conditions. Moreover, the Jarvik 7 is more effective in patients with multi-system organ failure than any left-ventricular assist device.
Another advantage of the Jarvik 7 is that it adjusts the pumping of the right and left sides of the heart independently, permitting optimal filling and ejection on each side. The AbioCor, on the other hand, alternately pumps the right and left sides, filling one while emptying the other. Its design does not permit independent right/left control and therefore can force blood into the lungs at an excessively high pressure, harming lung function. "Almost all AbioCor patients who survived the surgery have required respirators for a month or two," Dr. Jarvik says, "whereas Jarvik 7 patients are usually off the respirator within a few days."
The main drive console used with most Jarvik 7 patients is large, but it is actually smaller than the console used with more than a thousand Thoratec device patients. Although the main console is not suitable for a truly mobile lifestyle and presently is limited to in-hospital use, a small, portable, battery-run power system has been developed for the Jarvik 7 and used in patients — like Mr. Schroeder — outside the hospital. With modern lithium-ion battery technology, a portable power unit could feasibly be built weighing about 8 pounds and lasting several hours between battery changes. It would be the same weight as the AbioCor battery and electronics components.
A significant advantage of the AbioCor is that it is much quieter than the noisy Jarvik 7, which has four mechanical heart valves. By contrast, the AbioCor uses quiet trileaflet plastic valves. Also, the two tubes that provide compressed air to power the Jarvik 7 heart are a potential source of infection, especially in long-term use (meaning 2-5 years or more). With careful management, they were not a serious problem in the Jarvik 7 (CardioWest) clinical trial: There were 17 driveline infections in 81 patients, most of which were superficial skin infections treated with routine dressing changes.
The AbioCor, though, is designed with no drivelines penetrating the skin. Rather, it uses radio-frequency transmission of power from an external transmitter coil (about the size of a CD case) to an implanted receiver coil. Although this design may prevent infections associated with wires piercing the skin, Dr. Jarvik and others note its serious drawbacks:
"A further advantage of the Jarvik 7 heart," Dr. Jarvik adds, "is that it fits in more than 90% of the U.S. population, both men and women. By contrast, the AbioCor fits in less than 10% of the population and only a few percent of American women."
The data table below compares the initial Jarvik 7 patients with the initial AbioCor patients. It only includes the first seven patients because, at the time of this writing, data on the later Jarvik 7 patients is not available.
"With all the effort expended and complex modern technology used, the AbioCor has not achieved better results than the Jarvik 7 did twenty years ago," Dr. Jarvik says. He points out that the Jarvik 7 patients survived longer, with better quality of life, than the AbioCor patients. No Jarvik 7 patients died at surgery, but two AbioCor patients did. No Jarvik 7 patients died of device failure, but two AbioCor patients died as a result of mechanical failures. Both devices had a serious problem with stroke in the early patients, which was greatly reduced in later Jarvik 7 patients. Abiomed made changes in the design intended to avoid strokes, but patients continued to have them.
"Not to mention," Dr. Jarvik adds, "that present results with the Jarvik 7 (CardioWest) are much better than the initial results many years ago."
Click table for larger view.