CDU

In 1982, physicians at the University of Utah (Salt Lake City, Utah) implanted the Jarvik-7 mechanical heart in the chest of Barney Clark. While the procedure was widely hailed by the press as the first "successful" use of a totally artificial heart, the device served to prolong Clark's life for just 112 days, much of that time spent fending off agonizing and debilitating infections and other complications. Since then, there have been more than 200 implantations of artificial hearts using about a dozen such devices, with none being able to supplant the real thing for significant periods or provide a sustained improvement in the patient's life. As a result, while the artificial heart continues to generate sporadic interest in the popular media, in the field of cardiology it is a Holy Grail of somewhat dubious value.

Perhaps one of the reasons that the total artificial heart – sometimes referred to as a double pump heart – has been so elusive is that all of the devices thus far developed have been, of necessity, fairly complicated, according to Bartley Griffith, MD, who himself implanted some of the Jarviks in the early 1980s. Currently he is director of the McGowan Center for Artificial Organ Development, a unit of the University of Pittsburgh Medical Center (UPMC; Pittsburgh, Pennsylvania), focused on developing not only substitutes for the heart, but for the lung and other organs as well. "The funny part is that the heart is a rather simple organ, probably the dumbest organ of the body," Griffith told Cardiovascular Device Update. "It's just a muscle – but it has to work all the time." And, he added, the healthy heart also has the instinctive ability to change speeds, frequently and rapidly, perhaps the most difficult part of its action to reproduce mechanically.

While these basic abilities in a completely artificial heart have yet to be accomplished, the challenges they present have had the benefit of leading researchers to develop a whole range of new technologies and systems to learn more about the heart and to develop new forms of protection and support for it. Among the most important of these is the development of single-pump left ventricular assist devices (VAD) that replace not the entire heart but its most important activity: simply pumping. A whole range of such devices has been developed, with the smallest and lightest of these being the recently unveiled Micromed DeBakey VAD, produced by MicroMed (Houston; Texas), reported on in last month's issue of CDU. But like implantation of a total artificial heart, the implantation of a VAD is highly invasive and remains largely a sort of stopgap or bridge to transplantation.

The 'dumb' pump and computer intelligence

In the meantime, researchers are putting increasing emphasis on a whole range of less invasive technologies to avoid the need for a VAD, a total artificial heart or a heart transplant. Happily, VAD development and continued pursuit of the total artificial heart are being supported by leading edge technologies – primarily the computer and its ability to run complex algorithms – broadening understanding of this "dumb" pump, supporting it when it gets sick and attempting to keep it healthy.

One of the most intriguing of these new technologies is the BioZ system from CardioDynamics International (San Diego, California). As a relatively new monitoring technique that is providing more information about hemodynamics, or the fluid mechanics of the heart, the BioZ system is being developed by CardioDynamics to be a common, non-invasive tool to better understand how the heart handles blood and what happens when it fails. Specifically, the company wants to both add this tool to the primary care physician's armamentarium for treating the heart and expand its use by cardiologists, according to Michael Perry, CEO of CardioDynamics.

"Until recently, hemodynamics only has been available in the hospital," via pulmonary artery catheterization, he told CDU. He characterized that procedure as "an invasive, even a gruesome procedure," and one that is "very risky, very costly to the health care system."

But apart from this risky, occasionally fatal and expensive technique, he says the general physician can measure hemodynamics only with traditional and fairly crude clinical methods to manage medication and overall treatment of congestive heart failure: these are "the blood pressure cuff, the physical exam and a series of questions: 'How are you feeling? How does this compare to the last time you were here? And so on.'" And, Perry pointed out, "In this world of high-tech surgical techniques, it's quite amazing that this procedure is not much more than what was available in the 1800s."

Offering the potential for greater simplicity – and certainly a less-invasive approach – BioZ monitoring is a system of impedance cardiography (ICG) that is objective, noninvasive and faster, all factors that have been validated by what Perry called "a groundswell of clinical evidence." The company previously received approval for its professional BioZ.com system for hospital settings. In late June, it received clearance for its BioZ.pc, a laptop system that greatly expands the product's market potential by making BioZ available at an important point of care, the physician's office.

Explaining how BioZ compares to another common monitoring modality, Perry said, "The EKG is a 10-lead configuration and sometimes 5-lead. The BioZ consists of four sets of dual sensors, two on the neck, two on the chest. We pass an injectable high-frequency, low-amplitude current through the chest cavity. Since blood is the most conductive substance in the chest, and with every contraction of the heart, you get a change of impedance or conductance called impedance waveform." That waveform is then analyzed to produce 12 parameters of heart performance – such as liters of blood per minute, fluid content in the thoracic area, vascular flow resistance, liters per minute and others – combined via CardioDynamics' algorithms to give a clarified view of how a heart is handling its blood, and thus a better guideline for therapy.

The newly approved laptop system in essence provides access to the company's professional installation and creates a synergy between the two: the larger infrastructure of the system supporting the laptop users and the laptop users providing expanded feedback concerning system parameters for potential therapeutic options. According to Perry, BioZ.pc "serves as the user interface that attaches to our measurement circuitry and algorithms. It functions in a larger, Internet-based information management solution. We take the results that are pulled off of our systems, transmit them to a central file server. The server is accessed via the Internet from the physician's office and a report is e-faxed back to them with all the relevant hemodynamic measurements on it."

Market maturity means education

Through installations of the professional system, CardioDynamics is beyond the early development stage but has a ways to go before realizing market maturity, Perry acknowledged. He said the key to that eventual maturity is essentially educational, with the company's target being the general practitioner and family physician. "The cardiologists understand hemodynamics and are using our systems. Now we have to tell our story to the non-specialists. But that will come." Ultimately, Perry added, the goal is to make BioZ monitoring as ubiquitous as blood pressure cuffs. "This is a new tool in a setting where [physicians] are not used to having this information. What we must do is teach them what to do with it," he said.

That effort offers "two primary segments," he said. "One is the currently monitored – that's about two million around the world in hospitals today. Our larger market is 50 times that size, or 100 million non-invasive procedures done around the world."

Besides offering assessment of heart function, BioZ is a platform technology that can be integrated into other systems, and last month CardioDynamics reported an agreement with GE Marquette Medical Systems (Milwaukee, Wisconsin) for integrating BioZ into that company's Solar patient monitoring systems. The agreement expands CardioDynamics' relationship with GE Marquette, giving that company exclusive rights to market BioZ products through the U.S. and several international markets. Perry called the agreement "the next important step in our strategy to compete aggressively in an estimated $2 billion non-invasive hemodynamic monitoring hospital market."

Fibers, fiber optics, wearable sensors

While BioZ can deliver more information to the physician's office, other techniques are being developed to generate information about the heart at the true first point of care: the individual going about daily activities at home and work. This can be achieved in part by Holter monitoring and some of the VAD devices, but a researcher at the Georgia Institute of Technology (Atlanta, Georgia) has taken this idea even further – beyond a seemingly sci-fi proof of concept to everyday wear, as it were. The product is a "smart shirt" or, more precisely, the material used to make such a shirt. This wearable monitoring system is the brainchild of Sundareyan Jayaraman, PhD, a professor in Georgia Tech's School of Textile and Fiber Engineering.

Referring to the recent successes of the genome project, Jayaraman acknowledged their importance but said a greater near-term accomplishment is monitoring of the heart's everyday activities to provide "a rich source of data, acquired continuously, concerning how the body acts in real situations," he told CDU. While it may take from 10 to 20 years or more to turn the benefits of gene mapping into commercialized products, achieving this rich data stream may be made as ubiquitous as, literally, the shirts on our backs, based on Jayaraman's work in combining sensor technology with leading-edge fibers and fiber optics.

Earlier this year, Jayaraman unveiled a fabric interwoven with plastic polymer optical sensors and then made into a basic T-shirt. Dubbed the Smart Shirt, the special optical fibers in the material can provide an ongoing stream of vital sign information while a person goes about his or her day-to-day activities. The challenge to develop this type of clothing monitor first came from a U.S. Navy grant, but Jayaraman said he soon realized that the concept's greatest benefits would be in its potential health care applications, from shirts worn by congestive heart failure patients to pajamas for infants at risk for sudden infant death syndrome.

These and other broad applications for the material are being developed through an agreement between the Georgia Tech Research Corp. and SensaTex (New York), a startup company funded by Seed One Ventures (New York). Jeffrey Wolf, CEO of SensaTex, calls the shirt essentially a "wearable motherboard, providing information from a wearable environment." An additional key to the system is its wireless technology. "You can monitor patients, for instance, with a Holter monitor, without wires down through patient's body," he told CDU. "It also means that you can integrate additional sensors to get even more information than you can get now because of reducing the need for wires, and you can have these [sensors] speak to one another."

SensaTex will seek FDA clearance through a 510(k) application, with the shirt and its optical wiring developed as a platform technology offered to other companies whose specific applications have already been approved. Wolf said he sees the Smart Shirt's commercialization as early as 1Q01.

Besides monitoring heart patients and others at risk, the next most usable application will be in monitoring subjects participating, for instance, in clinical trials to continuously read their reactions to drugs or devices; for measuring sports performance; and in geriatrics. These can then be expanded to a wealth of uses in the military, police and fire protection. The Smart Shirt's ability to produce accurate, real-time results, Wolf said, "represents a quantum leap in healthcare monitoring, The potential applications for the technology are enormous .... and SensaTex is well poised to pursue them all."

Cholesterol, smart cards and the Internet

Another company using a new "smart" system is Lifestream Technologies (Post Falls, Idaho) which is combining encrypted Smart Cards, using Microsoft (Redmond, Washington) technology, with the Internet to take on cholesterol, one of the major enemies of the healthy heart. While many diagnostic enterprises identify the doctor's office and the bedside as key points of care, Lifestream Technologies is on a mission to give point-of-care power to the patient with basic credit card technology that interfaces with home testing devices, home and office computers, the entire system being web-enabled.

The system's initial focus is cholesterol, according to Christopher Maus, Lifestream president, because of how pervasive high cholesterol is among Americans, citing 98 million of us with elevated levels of the artery-clogging material. "We're looking at the biggest health care issue that the government has ever tackled," Maus told CDU. Calling elevated cholesterol a "hinge pin" connecting to hypertension and the full range of heart diseases, Maus said that this problem eventually "kills virtually every other person. It doesn't discern between gender or economic brackets or class. It is a big, big issue throughout all of society."

With the Lifestream Home Cholesterol Monitor and what looks like a credit card, individuals will be able to track their daily cholesterol levels at home with a single drop of blood inserted into the monitoring device. The device then produces a readout collected and stored on the card which is then usable in a variety of ways. The stored readings, for instance, are downloadable by both the individual and his or her doctor. More important, they provide a "rolling" record that can be used to assess 13 different risk factors and then generate both an analysis of those factors and a basic program for disease management that is continuous, not just the product of occasional tests and physician visits, Maus said.

Rather than being a clinical tool just for the doctor, the Lifestream smart card offers a system for behavior change. "The Lifestream system puts the emphasis on preventive health care," Maus said. And the information is readily available: "The patient doesn't have to carry around a book. Numerous studies have demonstrated that individuals who regularly test themselves while on a therapy program – such as obesity, hypertension, diabetes and elevated cholesterol levels – stay on treatment programs longer, with better results."

Like CardioDynamics, Lifestream first developed and received FDA approval for the professional version of its monitor, smart card and the supporting information system – which relies heavily on findings from the Framingham Heart Study. It is now awaiting approval of its consumer system, an over-the-counter product that will be priced at around $120 to $130.

Maus said the beauty of the smart card approach and peripherals is the creation "of a seamless medical device system, from a classic in vitro diagnostic device, through a PC, through the Internet and back again." The result is a system of information that, he said, can be used to produce "quantitative objective dialogue with the physician – and objective outcomes."

Electromagnetism and levitation

Perhaps the most intriguing use of new technologies for failing hearts is a system that returns us to our starting point: the pursuit of an ideal pump that both supports the flagging action of the heart and may serve as a path to a true total artificial heart. The key to such a system may be found in electromagnetic forces that can be used to sidestep the friction inherent in mechanical devices, according to Griffith of the McGowan Center for Artificial Organ Development.

"The Achilles heel of any pump is the need for a bearing, the necessary component for something to rotate on," Griffith said. "So any mechanical bearing is potentially a problem in a heart pump. It will wear out or 'clot off,' or something can land on that bearing and cause the pump to seize up. You have to eliminate the classic bearing, create a bearingless pump." You can accomplish this with an act of levitation, that job currently being tackled by the McGowan Center's partner, Vascor (Pittsburgh, Pennsylvania), the company that created one of the first cardioverter defibrillators, according to its president, Steve Kulenik.

"The blood pump consists of a rotating member that's not touching anything; it's simply rotating in space. Vascor has some dominant basic patents on magnetic levitation for blood pumps," Kulenik told CDU. This is done with opposing magnets and electromagnetic coils positioned in a stationary shell, levitating and spinning a rotor while also providing a way to control its speed. Besides these controls, the Vascor VAD will incorporate the firm's expertise in defibrillator technology to manage arrythmias and thus support the heart electrically as well as mechanically. Combined with these systems are specially designs for the axial flow of blood through the pump and the knowledge gained by the University of Pittsburgh Medical Center in handling blood in mechanical systems.

Excellent design work

"With blood," Kulenik said, "you have to really do excellent design work to make sure you don't damage the blood. If you damage blood cells, they can form clots, plug up the pump, break up and go into the body. So the incidence of stroke with mechanical hearts is very high. We think with [development help by] the University of Pittsburgh, we've been able to overcome many of these problems."

Vascor is in preclinical trials and expects to launch clinical trials in another two years, with hoped-for commercialization in 2004 or 2005 – a goal Kulenik described as "realistic." Vascor is pursuing development of the single-pump VAD first, he said, "because that's where 90% of the market is." But he also notes the increasing need for end-stage support of those patients who cannot be saved with only a ventricular-assist device. Thus, he hopes that following approval of the single-pump VAD, the double-pump product could come "one or two years after that."

Until then, however, Griffith refers to Vascor's work as "the Lexus of this new generation of pumps." And, he adds, what may be obvious to anyone seeking the ultimate in heart pumps: "This is a very interesting time."

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