Pre-clinical Testing of a VAD for Uni- and Bi-ventricular Support in Infants

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DESCRIPTION (provided by applicant): The long term objective of this research is to provide a Ventricular Assist Device (VAD) designed specifically for infants, who require mechanical circulatory support of left, right, or both ventricles. The use of VADs in adults has become a viable means of support in end stage heart disease, as a bridge-to-transplant, and more recently as destination therapy. However, the only devices currently available for infants are either limited in support duration (typically 1 month) or carry significant thromboembolic and bleeding risks. The specific objective of this project is to perform pre-clinical testing of the Pen State Infant VAD. The Penn State Infant VAD is a pulsatile pneumatically-actuated pump with a 12-14 ml stroke volume. The device has demonstrated low thrombogenicity in pilot animal studies, in part due to the custom Bjork-Shiley monostrut valves, as used in the Thoratec adult VAD. The monostrut valve does not exhibit the recirculation regions found behind the leaflets in polymer trileaflet valves. We have also developed an innovative approach to cannulae design, which has been a shortcoming in current pediatric VADs, and which is critical to reducing thromboembolic risk, especially in infants and in those with congenital anatomic variability. The primary objective of this project is to perform pre-clinical testing (in vivo and in vitro) of the enn State Infant VAD and new cannulae system, leading to a clinical trial. A secondary objective is to investigate the mechanisms of thrombus formation, thromboembolism in a VAD system, by testing of the Infant VAD over a wider range of pump flow and anticoagulation states than would normally be required for regulatory approval, using multiple measures of coagulation, platelet function, renal function, and explant analyses. This objective represents an opportunity to contribute to the broader field of circulatory support device development and the design of animal testing protocols, especially in regards to anticoagulation approaches. The specific aims are: 1) to perform pre-clinical testing in animals to assess thrombogenicity of the Infant VAD system utilizing the 15-25 kg lamb model in 60 day chronic studies, 2) to assess the thrombogenic potential of the Infant VAD system in weaning mode, in which the VAD flowrate is reduced, and 3) to demonstrate reliability of 0.80 with 80% confidence for a six-month system design, with testing to demonstrate device reliability by sustained operation for periods at least twice as long as the intended use (i.e. one year).