Pediatric Cardiac Assist Devices in Evolution

The development of long-term mechanical support devices for children has lagged notably behind that of adult devices. Miniaturization of device components and cannulas imposes significant technical and engineering challenges, further complicated by the need for application in a wide range of patient sizes. Perhaps more important, there is little financial incentive for private industry to invest in the development of products with a relatively limited potential market. In addition to the cost of research and development, the complexity and expense of the US Food and Drug Administration (FDA) approval process may be prohibitive. The only device to attain FDA approval before 2011, the DeBakey VAD Child (MicroMed Cardiovascular, Inc., Houston, TX), is limited to use in older children.

The Berlin EXCOR VAD was developed at the German Heart Institute Berlin and has been used in Europe since 1990. The device consists of a paracorporeal pneumatically driven ventricle connected to the heart by inflow and outflow cannulas that exit the abdominal wall. The ventricles are available in a range of sizes, allowing long-term left ventricular assist device (LVAD), right ventricular assist device, or biventricular assist device (BiVAD) support in patients as small as 3 kg. Beginning in 2000, permission for compassionate use of EXCOR was granted on a case-by-case basis for pediatric patients in the United States. Despite the relatively large number of patients treated worldwide, the lack of systematic and standardized safety information, particularly with regard to anticoagulation regimen and stroke risk, precluded FDA approval on the basis of historical data. A multicenter FDA investigational device exemption study was therefore designed to assess the safety and efficacy of EXCOR as a bridge to transplantation. Enrollment of 48 subjects began in 2007, and results were compared with those from historical ECMO controls. Median survival was 110 days with EXCOR compared with 10 days with ECMO. Adverse events with EXCOR included major bleeding in 46%, infection in 57%, and stroke in 29%. Ninety percent of subjects survived to transplantation or to weaning from the device. On the basis of these data, EXCOR received FDA approval through the humanitarian device exemption process in December 2011. A postapproval study is currently in progress to confirm the findings of the investigational device exemption trial.

Simultaneous with the increased use of EXCOR, in 2002, the National Heart, Lung, and Blood Institute initiated a program to develop improved long-term cardiac assist devices for use in small children. The Pediatric Circulatory Support Program solicited contract proposals for novel bioengineered systems for children between 2 and 25 kg. The initiative specified technical requirements to overcome the shortcomings of currently available devices, including (1) the ability to deploy and implement in <1 hour; (2) minimizing priming volume; (3) cannulation able to accommodate variations in patient anatomy; (4) minimizing exposure to blood products; (5) minimizing the risks for infection, bleeding, hemolysis, and thrombosis; and 6) allowing support for up to 6 months. Thirteen proposals were reviewed, and in 2004, 5 grants totaling $22.4 million were awarded for use over 5 years.

The funded proposals constitute a variety of approaches to long-term pediatric cardiac support. The PediaFlow VAD (WorldHeart Corporation, Salt Lake City, UT), developed at the University of Pittsburgh, is an implantable, mixed-flow turbo magnetic rotary blood pump for patients 3 to 15 kg in size. The PediPump VAD, developed at the Cleveland Clinic Foundation, is an implantable magnetic bearing-supported rotary circulatory pump that can be deployed in an intravascular or extravascular position depending on patient size. The Pediatric Cardiopulmonary Assist System proposed by Ension, Inc. (Pittsburgh, PA) is a paracorporeal rotary pump-oxygenator device that is essentially a miniaturized ECMO circuit. Multiple sizes will allow use in children of all ages. Jarvik Heart, Inc. (New York, NY), the manufacturer of the first successful adult artificial heart, proposed the Pediatric Jarvik 2000, an axial-flow blood pump that can be implanted in any cardiac chamber for assist. Infant (3–15 kg) and child (15–25 kg) models are based on modifications of the previously developed adult model. Finally, a pediatric VAD developed at Penn State is a pulsatile pneumatically actuated blood pump that is a modification of the Thoratec VAD (Thoratec, Inc., Pleasanton, CA) currently used in adults. Infant-sized and child-sized devices will be designed for paracorporeal or preperitoneal implantation. All proposals included unique engineering, materials, and design specifications to meet the technical requirements outlined above. A preliminary report published in Circulation in 2006 indicated promising early success in basic model design and development. The Pumps for Kids, Infants and Neonates (PumpKIN) program was established by the National Heart, Lung, and Blood Institute in 2010, providing another $23.6 million to fund preclinical testing of the University of Pittsburgh, Ension, and Jarvik devices as well as one additional device not included in the Pediatric Circulatory Support Program. Results will be used to support applications to the FDA for clinical trials in 2014.