A tiny heart pump that maintains blood flow in babies and small children with serious heart failure proved effective and life-saving in a pioneering study involving 17 institutions led by Texas Children's Hospital and Baylor College of Medicine. A report on this study appears today in the New England Journal of Medicine.

The study looked at the safety and probable benefit of the Berlin Heart® EXCOR Pediatric Ventricular Assist Device, the only VAD available for babies and children. Patients who received the Berlin Heart lived longer on the device and were more likely to receive a transplant or recover heart function than children who were maintained on more traditional support using extracorporeal membrane oxygenation (ECMO), according to the study's results.

"This study is unprecedented and represents broad collaboration among the top pediatric cardiac transplantation centers in North America, really the who's who in the field," said Dr. Charles Fraser Jr., surgeon-in-chief at Texas Children's Hospital and professor of surgery and pediatrics at BCM. Fraser is also the corresponding author of the report and was national principal investigator of the study. "This study is now the gold standard for VAD therapies in children. Everything going forward will be compared to this."

Before the Berlin Heart

Before the Berlin Heart, physicians used complicated medical therapies to treat children with heart failure, hoping to keep them alive until a suitable donor heart became available. Newborns and small children often died as they waited since no more than 70 or 80 small donor hearts become available each year. ECMO provided only short term support when the child's heart failed completely. The Berlin Heart offers families a new ray of hope.

"With the Berlin Heart, we have a more effective therapy to offer patients earlier in the management of their heart failure," said Fraser. "When we sit with parents, we have real data to offer so they can make an informed decision. This is a giant step forward."

Children on the device can leave the intensive care unit and go to a regular hospital room where they receive rehabilitation and better nutrition while they wait for a transplant. While there are many such devices available for adults, development and approval of devices for children and especially for babies has lagged.

Prospective study

"This prospective trial is unprecedented because it was not a look back at how children on the device had fared but instead followed their clinical course from the device's implantation. The results were compared to those of children who received ECMO, the only other method of treatment," said Fraser, also chief of congenital heart surgery at Texas Children's.

"We thought we knew a lot about this device and how it worked, but the FDA was insistent that we conduct a trial and they were right. We did not know as much as we should about how the device performs in practice."

Higher survival rate

For example, he said the survival rate with the device is higher than anticipated and so was the stroke rate. While the stroke rate was of concern, residual effects from the stroke did not prevent most patients from receiving a transplant, the researchers note.

The Berlin Heart is not totally implanted inside the body. Physicians insert cannulas, or flexible tubes, in the heart and they extend through the skin and connect to a small pump located outside the body. That pump, along with its computerized drive unit, maintains blood flow.

Fraser and his colleagues in the United States and Canada compared the outcomes for 48 children (infants to 16 years) who received the device between 2007 and 2010 to matched patients in a national registry for those patients supported by ECMO. They divided the patients who received the German-manufactured heart assist device into two groups based on their body size.

Those in the cohort of smaller patients (average age 1 year) survived on the heart for a median time of 28 days compared to five days for the children on the ECMO device. The longest time a child in this cohort was on the Berlin Heart was 174 days compared to 21 days for the ECMO group. At 174 days, 88 percent of the children in the cohort had been successfully transplanted and 12 percent had died or failed weaning. In the comparison group, 25 percent of the children had died at 21 days and none were still on the ECMO device.

For children in the second cohort with a larger body size (average age 9), the median survival on the Berlin Heart was 43 days compared to five days for the ECMO group. The longest a child stayed on the assist device was 192 days; the longest a member of the matched group was on ECMO was 28 days. In the device group, 92 percent of the children who had received the VAD had been successfully transplanted or weaned off the device at 192 days and 8.3 percent had died. In contrast, 33 percent of the children in the ECMO group had died at 30 days and none were still on that device.

Some children did suffer serious side effects, including major bleeding, infection stroke and high blood pressure. These findings are as important as the survival statistics because they set the stage for future development and refinement of these devices, said Fraser.

Humanitarian Device Exemption approval

The Berlin Heart EXCOR Pediatric Ventricular Assist Device was approved by the U.S. Food and Drug Administration (FDA) for use in children in 2011. That allows the device to be used as a bridge to transplantation. The Berlin Heart has been used in approximately 1,000 children worldwide.

It assists the ventricles ­ the pumping chambers of the heart ­ in circulating blood throughout the body. In most children with heart failure, the left ventricle fails and the device is used to assist its activities. However, in a few instances, two devices are used to replace both chambers of the heart. This pump is available in a variety of sizes.

Without the assistance of the device, children awaiting a transplant would become increasingly sick as their heart failed. The device improves their circulation and keeps them alive until they receive a heart transplant. In some rare instances, patients recover enough to come off the device and maintain blood flow on their own.

Fraser first used pump seven years ago

Fraser first used the pump in an infant ­ tiny Brady Burch of Corpus Christi ­ seven years ago. Brady, now 7, went on to receive a transplant and enters first grade this fall. The success with Brady stimulated Fraser to push for a study of the device to determine its effectiveness.

Fraser said a major limitation of the study is that it is not truly randomized ­ a method by which patients are assigned an experimental treatment or currently accepted treatment by chance, as in the flip of the coin.

"There was no way we were going to randomize patients. Even using ECMO as a comparison was difficult," Fraser said. They drew their comparison patients from the Extracorporeal Life Support Organization registry based in Ann Arbor, Michigan. They matched each patient who received the Berlin Heart to two closely comparable individuals in the registry. While using these historical control patients was difficult, it was the only ethical method of obtaining comparison, Fraser said. He believes the study will provide important information for the future.

"I don't think we are far from a small, implantable VAD in children," he said. "The implantable devices will be less cumbersome. There are approved, fully implantable devices already available for adults. This gives us the drive to push even further for more devices like this that can be life-saving options for these children who have no other treatment options."

Texas Children's Hospital implanted more Berlin Heart devices in the course of the study than any other center and has one of the most comprehensive pediatric ventricular assist device programs in the world.

Others who took part in the study include Drs. Robert D.B. Jaquiss of Duke Children's Hospital and Duke University School of Medicine in Durham, North Carolina; David N. Rosenthal of Lucile Packard Children's Hospital and Stanford University School of Medicine in California; Tilman Humpl of the Hospital for Sick Children and the University of Toronto in Canada; Charles E. Canter of St. Louis Children's Hospital and the University of Washington in St. Louis, Mo.; Eugene H. Blackstone of the Cleveland Clinic and Lerner College of Medicine Of Case Western Reserve University in Cleveland, Ohio; David C. Naftel and F. Bennett Pearce, of the University of Alabama School of Medicine; Rebecca N. Ichord of Children's Hospital of Philadelphia and Perelman School of Medicine of the University of Pennsylvania in Philadelphia; Lisa Bomgaars and Kathleen E. Carberry, RN, MPH, of Texas Children's; James S. Tweddell of Children's Hospital of Wisconsin and Medical College of Wisconsin in Milwaukee; Patricia Massicotte of Stollery Children's Hospital and University of Alberta School of Medicine in Edmonton, Alberta; Mark W. Turrentine of Riley Hospital for Children and Indiana University School of Medicine in Indianapolis; Gordon A. Cohen of Seattle Children's Hospital and University of Washington School of Medicine in Seattle; Eric J. Devaney of C.S. Mott Children's Hospital and University of Michigan Health System in Ann Arbor; Robert Kroslowitz of Berlin Heart Inc., of The Woodlands Texas and Christopher S. Almond of Children's Hospital Boston and Harvard Medical School.

Funding for this study came from the U.S. FDA's Office of Orphan Product Development and Berlin Heart Inc.

Dr. Fraser holds the Clayton Chair in Surgery and the Donovan Chair in Congenital Heart Surgery at Texas Children's Hospital and is professor and chief of the division of congenital heart surgery in the Michael E. DeBakey Department of Surgery at BCM.