$4.5 million contract to develop heart assist devices for infants

The University of Pittsburgh's McGowan Institute for Regenerative Medicine has been awarded a five-year $4.5 million contract from the National Heart, Lung, and Blood Institute to develop a heart assist device for infants.

Working with Children's Hospital of Pittsburgh, Carnegie Mellon University and industry partners, the Pitt researchers envision the pediatric ventricular assist device (PVAD) to be about the size of a quarter, with features designed to meet the special needs of patients with congenital and acquired heart defects who are as young or small as a newborn baby.

Principal investigator for the contract is Harvey S. Borovetz, Ph.D., professor and chairman, department of bioengineering, University of Pittsburgh School of Engineering, and Robert L. Hardesty Professor of Surgery at the School of Medicine.

The only means of mechanical support currently available in the United States for infants and children up to age 2 is ECMO, or extracorporeal membrane oxygenation, which can only be applied for up to several weeks and completely immobilizes patients with its elaborate network of tubes and medical equipment.

Despite it being standard practice for nearly 30 years for pediatric patients of all ages who are in heart failure, its use is associated with a high death rate. Less than half of children and infants survive the therapy. Larger children sometimes have the option of being supported by ventricular assist devices (VADs) that have been designed with the adult patient in mind, but no devices currently approved by the U.S. Food and Drug Administration are small enough to be implanted in infants. "Historically, infants and toddlers have been overlooked by technology development. Yet the smallest of our patients have the greatest need because the only means of support available to them is ECMO, which has unacceptably high mortality and complication rates. We hope to be able to develop a device that will allow more babies with congenital heart defects or end-stage heart disease to survive to transplantation, or perhaps even recover cardiac function and avoid the need for transplantation," said Dr. Borovetz.

To develop the PVAD, Dr. Borovetz has assembled a multidisciplinary team of bioengineers, surgeons and researchers from Pitt's schools of Engineering and Medicine and the McGowan Institute for Regenerative Medicine.

Working as subcontractors will be pediatric cardiologists from Children's Hospital of Pittsburgh, bioengineers from Carnegie Mellon University and research teams from MedQuest Products, Inc., of Salt Lake City, which hopes to manufacture and commercialize the device, and LaunchPoint Technologies of Goleta, Calif.

Researchers from Primary Children's Medical Center and LDS Hospital, both in Salt Lake City, also are involved. The goal of the contract is to develop a miniature centrifugal flow pump utilizing suspended magnetic levitation technology for use in babies between 5 and 35 pounds. It's conceived that the device could be used for up to six months as a bridge to heart transplantation.

In some babies, the device may allow the heart to recover. As such, the team plans to develop a smart control system that will indicate patterns consistent with a recovering heart. Since the device will be fully implantable with a small lead to an external power supply, children supported by the device will be able to be mobile and active.

The technology being applied to the development of the PVAD builds on the innovative work of James F. Antaki, Ph.D., associate professor of biomedical engineering and computer science at Carnegie Mellon University and associate professor of bioengineering and surgery at the University of Pittsburgh. Dr. Antaki is a co-investigator and the project director for the contract. "Our primary objective is to develop a highly reliable circulatory assist device for infants who would otherwise perish from heart failure," said Dr. Antaki. "This contract will enable our collaborative research team to apply over two decades of experience with cardiovascular support to design a novel device for this high-risk population. We aim to perform our first clinical trials within five years." Under the direction of Robert L. Kormos, M.D., director of the University of Pittsburgh Medical Center (UPMC) Artificial Heart Program and one of the project's co-investigators, there have been more than 275 implants of VADs at UPMC since 1985, including implants in 13 children between the ages of 7 and 17. Of these children, eight survived until a donor heart became available and two recovered while on the device. One patient is currently on a device awaiting a transplant. "The PVAD must be more than just a smaller version of the adult devices. It also must be designed to meet the special medical and circulatory needs of infants with complex congenital heart disease," noted Bradley B. Keller, M.D., professor of pediatrics at the University of Pittsburgh School of Medicine and chief of cardiology at Children's, and principal investigator for the Children's Hospital subcontract.

Also playing a key role for Children's is Steven Webber, MBChB, associate professor of pediatrics at the University of Pittsburgh School of Medicine and medical director of Heart and Heart/Lung Transplantation at Children's; and Sanjiv Gandhi, M.D., assistant professor of surgery, division of pediatric cardiac surgery, at the University of Pittsburgh School of Medicine. "As surgeons, physicians, bioengineers and bench scientists, we have different perspectives to the challenge at hand. But then, this interdisciplinary PVAD effort exemplifies the kind of collaboration that has existed for nearly 30 years at the University of Pittsburgh. We happen to believe it's the best way to solve problems in the clinical setting," added Dr. Kormos, who also is medical director of the McGowan Institute, where much of the research and development of the PVAD will occur.