Results of the study, which took place in Europe from October 1999 to December 2002, were presented Sunday, Nov. 9, 2003, at the American Heart Association's 76th Scientific Sessions conference, held in Orlando.
"This study suggests that fully-implantable mechanical heart support is possible and reliable," said John P. Boehmer, M.D., associate professor of cardiology, Penn State Cardiovascular Center, Penn State Milton S. Hershey Medical Center, who presented the results. "Only three device failures were recorded in 17.3 years of support time. We'll continue to improve upon that already-impressive record with device refinements and experience."
The trial of the left ventricular assist device, called the Clinical Utility Baseline Study (CUBS), included 23 male patients from Europe between the ages of 49 and 74 years with end-stage heart failure who were not candidates for heart transplantation. Patients with heart failure have a poor quality of life and low probability of surviving six months. The study was meant to determine the safety and performance of the LionHeart as a permanent method of circulatory support.
In the study, 10 of the 23 patients were released from the hospital. Forty-five percent of patients lived six months with 41 percent living 12 months and 34 percent living 24 months. On average, patients lived about nine months with the device, with one patient living more than three years. Three patients are still living (as of Nov. 1, 2003.) Two blood sacs failed after two years, which is the expected life of the sac, and one motor controller failed. A number of patients had some neurologic dysfunction and bleeding, and five experienced infections.
The LionHeart study results can be compared to the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of the Thoratec Corporation Heartmate*, a left ventricular assist device that requires cables that run from the inside of the body, through the skin, to the external power source. (NEJM, 2001;345:1435).
The rate of sepsis, or major infection, was .60 per patient year in the REMATCH trial, and only .17 per patient year in the LionHeart trial. That means that, each year, a patient had a 60 percent chance of major infection with Heartmate, and only a 17 percent chance of major infection with the LionHeart. In the LionHeart trial, there were no deaths due to infection related to the device as opposed to 20 deaths related to device infection in the REMATCH trial.
Local infection rate was .39 per patient year in the REMATCH trial, and .17 per patient year in the CUBS trial of the LionHeart. The device infection rate was .41 per patient year in REMATCH, and .17 per patient year in CUBS. Infection in the pump was .23 in REMATCH, and 0 in CUBS.
"LionHeart had a lower infection rate than other heart assist devices that require lines or cables protruding through the skin," said Walter E. Pae, Jr., M.D., professor of surgery, Penn State Milton S. Hershey Medical Center and principal investigator for both the U.S. and European trials. "Because there is nothing through the skin, it also allows patients to detach from the power source for short periods to bathe or swim, improving their quality of life."
When looking at how the devices functioned, the REMATCH trial reported a rate of malfunction of .75 per patient year for HeartMate. The CUBS trial showed a rate of malfunction in the LionHeart of .34 per patient year.
"Importantly, no one during the whole CUBS trial had to have a pump changed during the duration of the trial, whereas pump changes were not infrequent during the REMATCH trial," Pae said.
The rate of serious adverse events with the LionHeart compared favorably to the overall adverse event rate reported in the REMATCH trial. Boehmer noted that the CUBS trial of the LionHeart represented the initial experience with the device, while HeartMate had been implanted in the bridge-to-transplant application more than 2,000 times prior to the REMATCH trial.
Nearly 5 million Americans have heart failure and an estimated 400,000 to 700,000 new cases of heart failure are diagnosed each year. Only a fraction of those are eligible for and receive heart transplants.
Currently, a Phase I U.S. trial of the device is underway. Gayle Snider, a 36-year-old man from York, Pa., was the first U.S. recipient of the Arrow LionHeart released from the hospital. He recently celebrated four months at home and five months with the left ventricular assist device. Since leaving the hospital June 24, 2003, he has gained weight and taken a trip to the beach with family and friends. Most recently, Gayle enjoyed his favorite pastime - watching car racing - at the Dover Downs racetrack where he was treated to a behind-the-scenes look at a NASCAR event. (For more information, visit www.pennstatelionheart.com)
Arrow International, Inc., of Reading, Pa., announced Friday, Nov. 7, 2003, that it received authorization from its European Notified Body, TUV Product Services of Munich, Germany, to CE-mark the Arrow LionHeart, based on the results of the European trial. The CE-mark provides authorization to market the device within the European Economic Area for permanent implantation or "destination therapy". The Arrow LionHeart is the first left ventricular assist system to receive CE-marking authorization specifically for destination therapy.
Study sites for the European trial were: The Herzzentrum NRW (The Heart Center) in Bad Oeynhausen , Germany Deutsches Herzzentrum Berlin; Policlinico San Matteo (San Matteo Polyclinic), Pavia, Italy ; Hospital La Pitié, Paris; University of Vienna Hospital; CHUV Hospital Vaudois, Lausanne , Switzerland; and Freidrich-Schieller Universitat, Jena, Germany.
The Arrow LionHeart is the first totally implantable left ventricular assist device capable of taking over the entire workload of the left ventricle. Energy from an external battery pack is transmitted across the intact skin to power the system and charge the implanted battery.
The surgery involves attaching a mechanical circulatory assist device to the patient's natural heart. At the beginning of the procedure, the surgeon creates pockets in the abdominal and chest walls to hold the blood pump assembly, the energy source to power the moisture-proof motor, motor controller and internal batteries. Then, the patient is placed on a heart-lung machine to keep blood circulating and oxygenated during the surgery, and tubes are placed to connect the patient's heart and main blood vessel to the pump. Electrical connections are made from the pump and internal coil to the internal motor controller. Once the LVAD is implanted, telemetry is used to monitor the unit. The rate of the pump is increased until the patient can be weaned from the heart-lung machine. The automatic control system is switched on and the pump completely turned on takes over operation of the patient's left ventricle creating a physiologically normal pumping heart.
In February 2001, Arrow announced that the device received FDA approval under the Investigational Device Exemption to begin Phase I human clinical trials. The first U.S. recipient of the LionHeart received the device on Feb. 28, 2001, at Penn State Milton S. Hershey Medical Center. On July 26, Penn State Hershey Medical Center reported that the first U.S. patient died.
Penn State College of Medicine has a long history of heart device development dating to the 1970s when William S. Pierce, M.D., started his groundbreaking research in artificial organ development. The technology behind Arrow LionHeart was developed by Penn State Milton S. Hershey Medical Center's multidisciplinary team from the Division of Artificial Organs led by Gerson Rosenberg, Ph.D., Design News 2002 Engineer of the Year. This is the first heart assist device to reach clinical trial that is powered by wireless electric transmission. This allows the system to be totally implantable, giving patients freedom to take part in a broader range of activities and live an improved quality of life.