The objective of this proposal is to develop a Total Artificial Heart (TAH) for infants and small children. The Pediatric TAH will provide total circulatory support for patients under 1 year of age in severe biventricular failure while awaiting heart transplantation. Waiting list mortality is higher in this group than in any other age group. Post-transplant mortality is also higher because of multi-organ failure while on the waiting list. Survival in patients with single ventricle anomalies is especially poor. We propose to develop a pulsatile pneumatically actuated TAH which will be implanted orthotopically and provide total cardiac support to the systemic and pulmonary circulations. An FDA-approved TAH for adults (Syncardia) has been effective in bridge-to-transplant applications, with survival to transplant and survival post- transplant similar to that of patients receiving left ventricular assist devices and patients not requiring support. The Penn State Infant VAD, and a portable pneumatic driver, have been developed under NIH contract and grant support. Through continuous improvements in manufacturing techniques and animal testing protocols, we have been able to progressively reduce the level of heparin anticoagulation to the point of eliminating anticoagulation after the first 2-3 post-operative weeks. There have been no strokes or clinical evidence of thromboembolism in any animal studies. Hematological and blood serum chemistry parameters, as well as evidence of renal infarction, are similar in VAD animals and in surgical shams. We propose developing a 12 ml stroke volume device for infants (similar to our existing Infant VAD) and a 25 ml stroke volume TAH for small children.
The Specific Aims are: 1. Complete the mechanical design of the 12 ml and 25 ml stroke volume Pediatric TAH. 2. Implement automatic control of TAH output and left-right balance 3. Characterize TAH hemodynamic performance in vitro by measuring pump output as a function of preload and afterload pressures, and measuring the index of hemolysis 4. Perform in vivo studies to evaluate thrombogenicity, hemodynamics, and automatic control function 5. Assess pump durability through in vitro real time durability testing. Although the number of patients that will benefit frm the Pediatric TAH is small, the availability of a safe and effective TAH for infants and small children would likely increase survival on the waiting list, as well as post- transplant survival, n this challenging group. The current alternatives which include surgical palliation, ECMO, and the EXCOR Pediatric VAD, have been shown to have significant limitations in these smallest patients, and the scarce availability of donor hearts in this group will remain a challenge.
The objective of this project is to develop a Total Artificial Heart (TAH) for use in infants and small children to support the systemic and pulmonary circulations as a bridge to heart transplant. Two pump sizes will be developed to cover patients ranging in age from birth to approximately 9 years. With currently available options, waitlist and post-transplant mortality is high for this small group of patients.