Two of the 20th century's most groundbreaking innovations, magnetic resonance imaging (MRI) and pacemakers, are largely incompatible – or "contraindicated," to use Michael Weiner's more accurate terminology. Weiner is chairman and CEO of Biophan (Rochester, New York), a startup firm which has focused on developing MRI-friendly pacemaker technology. In doing so, Biophan is using the teamwork of Raymond Damadian, considered the primary developer of MRI machines, and Wilson Greatbatch, a key player in early pacing technology, a partnership that seems especially appropriate historically.
A founder of Biophan, Greatbatch serves as a technical advisor and a member of the company's board. And Damadian has committed the lab space, equipment and expertise of Fonar (Melville, New York), the MRI manufacturing firm which he founded and heads and is credited with producing the first MRI machine in 1977.
The technical link between the two is Biophan's expertise, which Weiner says is in the creation of "the photonic catheter," a device that offers a translation of light and electrical energy, thus providing a way to substitute fiber optics for the traditional wiring of the pacemaker. Weiner says he got the first look at this possibility about three years ago when he accompanied Greatbatch to Akron, Ohio, for Greatbatch's induction into the National Inventors Hall of Fame, and they ran into Damadian, another renowned member of the hall. Damadian began talking about the need for such a technology and continued to pursue it, with Biophan now taking up the challenge.
Weiner enumerates a variety of problems with the wiring of pacing technology and the way in which fiber optics solves them. Metal wiring, he notes, acts like an antenna, and the intense magnetic field of an MRI machine can cause rapid heating inside the pacemaker so that it may interfere with its synchronizing function or even burn and scar the heart itself. Thus, the company's tests have shown the typical pacemaker lead heating up by 20 degrees centigrade in 20 minutes, while the temperature of fiber optic leads will increase only a half-degree in that same period. With traditional leads, the risks increase with the increasing power of newer MRI magnets, Weiner notes. And compared to metal leads, the fiber optic system of wiring offers another advantage in MRI imaging, says Weiner, because it is less likely to produce imaging artifacts.
Rather than generic fiber optics, those developed by Biophan are used in high-speed telecommunications, with the system also including a microprocessor and a semiconductor laser working to convert the pacemaker's electrical power into light and back again. The laser "fires a pulse strong enough to fire the heart," Weiner says, serving to maintain normal rhythm. He says the new system offers "MRI-safety and MRI-compatibility."
Weiner says Biophan is now poised to move into the regulatory phase with a 510(k) application sometime this year. Assuming eventual approval, Weiner acknowledges that MRI-friendly pacing still faces another high hurdle, this time in the marketing phase – convincing those companies making pacemakers that Biophan's systems should replace traditional leads. But he predicts that in the dog-eat-dog arena of cardiovascular technology, competitive advantage is likely to prevail. "We aren't sure who will align with us first," Weiner says. "We're anxious to find the company that has the willingness and interest to gain that advantage."
Beyond the opportunity in pacing tech, Weiner sees possibilities for the company's fiber optic systems in all sorts of implantable devices, with the increasing use of implanted insulin pumps the next most obvious targets. Biophan's efforts also are backed by about a dozen patents pending (see Product Pipeline, page 18), according to the company, including one for an implantable laser. In a statement, Damadian praised the development of Biophan's systems for eliminating the "safety concerns completely" in MRI/pacing compatibility. And Greatbatch said he was "excited to have my old friend, Dr. Damadian, involved in our efforts" as Biophan works to bring their two technologies together.
DeBakey LVAD is readied for trial
Billing it as the very smallest device in the heart pump assist sector, MicroMed (Houston, Texas) reported early in February that it would soon file with the FDA its protocol for a trial of the MicroMed DeBakey left ventricular assist device (LVAD), named for its inventor, famed cardiovascular surgeon Michael DeBakey, as an alternative to transplant. The application will thus extend the company's current ongoing bridge-to-transplant clinical trial.
The new trial will be called DELTA 1, according to Dallas Anderson, MicroMed president and CEO. DELTA is not an acronym, but rather suggests "difference, an important difference, if you will" and one "of great significance," he told Cardiovascular Device Update's sister publication, Medical Device Daily.
Anderson describes two such differences: the device's small size, one-tenth that of other LVADs; and its quiet operation. The device measures just 1" by 3" and weighs in at a mere 4 ounces, compared to 2 pounds and up for other LVADs, and can sit much closer to the heart. Its quieter operation is the product of its axial flow design developed with the assistance of National Aeronautics and Space Administration engineers in Houston who worked with DeBakey in the earliest developmental stages.
Unlike pulsatile devices – meaning mechanisms that create a sort of pulse or a slight pumping sound – Micromed's LVAD "doesn't have to vent air out of valves. It has one single moving part, an Archimedes screw," DeBakey told MDD.
In announcing impending filing of the trial protocol, Anderson and DeBakey focus their comparisons on the HeartMate LVAD developed by Thoratec (Pleasanton, California) which has a large lead in this arena, already having received approval for bridge to transplant in 1998.
Both MicroMed and World Heart (Ottawa, Ontario) – which also received 1998 bridge-to-transplant clearance for its Novacor device but lags in the competition – are hoping to benefit from Thoratec's REMATCH trial, which showed strong results in comparing the HeartMate to standard medical therapy. That trial was scheduled to get some very close scrutiny by the FDA's cardiovascular device panel early this month when it was to review Thoratec's PMA supplement application for use of the Heartmate device as an alternative to transplant.
Anderson credits Thoratec's HeartMate for advancing the science in this area and saving about three of every four patients in which it is implanted. "It does good work, but it's big, noisy and expensive," he says.
From the surgical point of view, the miniaturization offered by the DeBakey LVAD offers several advantages, its inventor notes. Implantation requires "less surgical dissection [and] less surgical tissue is harmed," DeBakey says, "and that has an effect both in terms of blood loss and in terms of subsequent infection."
Addressing the issue of infection, DeBakey and Anderson point to a relatively high rate of infection in Thoratec's REMATCH trial, about 28%. In comparison, implantation of the DeBakey LVAD has shown an infection rate of about 5%, they say. And they also note an extremely low rate of device failures, at about 3%, though they acknowledge that data as relatively short term.
Responding to MicroMed's analysis, a spokesman for Thoratec warns against an "apples to oranges comparison," such as differences in trial design and differences between patients who are candidates for transplant and the "no-option" patient pool of the REMATCH trial. Thus, he emphasizes the longer-term data that Thoratec has been able to gather, as well as very different types of patients in its trials. Patients in the REMATCH trial were primarily in their 60s, he said, while MicroMed's patients have been in their 40s and somewhat healthier, he contends. Adding to this a market argument, he points to Heartmate's market leadership in Europe, and its status as a "gold standard" device there.
In answer, Anderson contends that the adverse events reported from the REMATCH trial were closely associated with device design and function, not the patient profiles or trial protocols.
Assuming FDA acceptance of MicroMed's alternative-to-transplant protocol, the company will be on track for PMA clearance by the end of 2003 or early 2004, according to Anderson, about the same timeline it expects for clearance of the bridge-to-transplant indication. Alternative to transplant will give MicroMed entry to what he estimates is a 100,000 patient, $4 billion opportunity, with DeBakey terming that "a very conservative figure." And DeBakey adds, looking to the product horizon, "Once we get to the point of being able to treat patients with heart failure, the potential population is over 5 million."
That horizon also offers an important vision – that the DeBakey LVAD can allow the very sick heart to rest and actually recover normal function. Here the advantage of an LVAD over a replacement heart is that the LVAD procedure is reversible, meaning that the pump, in some patients, could be removed.
The rehabilitation of a very sick heart may come with the support of pharmaceuticals or new biologic therapeutics – such as the use of Chrysalin, also being researched by MicroMed. For some patients, DeBakey says, "you won't need an LVAD – you can get rid of the pump and you don't need a replacement heart."
More accurate cardiac diagnosis
Looking to create a niche in an existing diagnostic market, Inovise Medical (Newberg, Oregon) is developing the Cardiovise DEC system, a product aimed for release later this year. Cardiovise DEC uses digital electroacoustic cardiography (DEC) technology to combine electrical and sound information from the heart for more accurate and timely identification of coronary artery disease, left ventricular hypertrophy, acute coronary syndrome and heart failure.
"It's a separate test that attaches to an ECG," said company spokesperson Cathy Epley. "Cardiovise runs the DEC test. It will take the electrical information that comes from an ECG machine and it will add our own algorithms and sound. We also have a sound sensor that is used along with the standard ECG sensors."
The company bills Cardiovise as an affordable cardiac diagnostic method compared to existing diagnostic systems, such as echocardiograms, MRI or catherization. "Rather than create a new, expensive piece of equipment, you can buy our product two ways," Epley said. "You can buy it embedded into an ECG machine, and you can also buy an upgrade box that will attach to an [existing] ECG machine."
The company cites two key advantages for Cardiovise over other tools – its low cost and noninvasive nature. "We are trying to fit ourselves into this segment, because there really is nobody in that segment," Epley said. Although Cardiovise is a separate test, it uses the electrode placement of the ECG and can be performed at the same time as an ECG. Cardiovise leverages the ECG, for which 860 million are performed annually by over 500,000 devices at a cost of $17 billion. Based on that rate of ECG usage, Cardiovise could tap a market in excess of $1.6 billion.
"First you run an ECG, then you push a button and then our test is run," Epley said. "First you get a printout of an ECG, and then you get a printout of our test." The equipment includes disposable smart sensors that capture both heart sound and electrical information and advanced algorithm software that analyzes this information. Cardiovise also provides a graphical image of the heart that includes the size and location of infarctions.
The company said early clinical results reveal a significant improvement over ECG sensitivity. Inovise also said the product narrows the gap on poor diagnostic results for women vs. men.
The privately held cardiac diagnostic company raised $12.5 million in a round led by new investors MDS Capital Corp. and TAT Capital Partners Ltd. Also participating in the round were UOB Hermes Asia Technology Fund, Glastad Invest Ltd. and current investors. Inovise said the funding, which brings total equity investment in the company to $22 million, will be used for final product development, marketing and sales.Inovise was founded in 1997 by managers from Hewlett Packard's cardiology diagnostic division.
MedicalCV launches carbon valve
U.S. patients in need of a heart valve replacement now have another option, an artificial valve with a good deal of overseas support. MedicalCV (Inver Grove Heights, Minnesota) launched stateside marketing of its Omnicarbon cardiac valve at the Society of Thoracic Surgeons Conference in Fort Lauderdale, Florida, in late January. The device won FDA clearance last August, and the company reported its first U.S. implantations in January. The first patients implanted with the Omnicarbon valve were a 50-year-old man, a 52-year-old woman and a 45-year-old man.
"This company pioneered over 30 years ago a lot of the technology that has gone into mechanical heart valves," said MedicalCV CEO Blair Mowery said. "This company's history and technology predates Medtronic [Minneapolis, Minnesota]; it even predates St. Jude [St. Paul, Minnesota]." Formerly known as Medical Inc., the company's roots are planted in the area's cardiac surgery history, with current board member Richard DeWall, MD, a developer of the heart-lung machine, thus reflecting MedicalCV's standing in the industry. Sylvin Weinberg, MD, a former president of the American College of Cardiology (Bethesda, Maryland), sits on the company's scientific advisory board.
Sold outside the U.S. since 1984, the Omnicarbon valve features a monoleaflet tilting disc valve, a valve with a single hingeless pivoting disc, that uses pyrolytic carbon, a highly biocomparible material, in both its housing and disc. Mowery said its design does not have the fixed pivot recesses characteristic of a bileaflet valve, "which is marketed by St. Jude, the market leader." The bileaflet design creates recesses, a location for blood clot formation. In contrast, Omnicarbon's single curved disc is designed to provide central flow with the least obstruction and least blood flow separation.
"The flow pattern in the design much more closely mirrors the native aortic valve," Mowery said. "The bileaflet separates the blood stream into three different flows, and if you were to look at the native valve, you would see a predominant flow and a minor flow. Our valve is much closer to the native flow. And secondly, our valve has no recesses in the cage ... You have higher [thromboembolism] rates with a bileaflet because you get platelet aggregation in those recesses. A thrombis forms in there, and a thrombis always forms in the recesses in bileaflets."
The U.S. regulatory process took longer than the company would have hoped, the initial applications submitted seven years ago. "When we submitted to the FDA, they didn't believe our data, because they said that we don't believe that any mechanical valve can perform this well," Mowery said. "They did their own analysis, and they reached the same conclusion, even showing that our data was better than what we originally submitted." He added: "We're just trying to re-establish the momentum that this company tried to establish in the early 1970s when it was the pioneer of the mechanical heart valve. We're using the heart valve and the science behind that heart valve to leverage ourselves in other areas," Mowery went on: "And we'll use that as the lead-in. Our focus is the cardio-thoracic surgeon – we're just developing products and technology for that guy."
Avant scrubs TP 10 program
Failing to meet the primary endpoint in a Phase II TP10 study in adult patients undergoing high-risk cardiac surgery, Avant Immunotherapeutics (Needham, Massachusetts) has halted development of the product. The decision wipes out the adult Phase II trial and also two Phase IIb trials in infants undergoing cardiac surgery.