Development of a Miniaturized, Pediatric Continuous-Flow Total Artificial Heart with a Single Moving Part

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Project Summary Mechanical circulatory support (MCS) is already a standard therapy in adult patients with end-stage heart failure. In pediatric patients with congenital heart diseases (CHDs), however, no implantable devices are currently available. Congenital anomalies in pediatric patients can make it difficult to use ventricular assist devices (VADs) to sustain hemodynamics. While heart transplantation can be an ideal therapy, donor hearts suitable for small children are very limited. Although total artificial heart (TAH) is an alternative for complex cardiac anomalies, no pediatric TAHs exist, other than SynCardia's 50cc Total Artificial Heart that is under investigational device exemption clinical study. This device is smaller than their regular 70cc TAH but is intended only for patients with a body surface area (BSA) of ≥ 1.2 m2, i.e., that of an average 11-year-old. The goal of this proposal is to develop a pediatric TAH based on Cleveland Clinic’s continuous-flow TAH (CFTAH), designed for use in adult patients (R01HL096619). Similar to the adult CFTAH, this pediatric CFTAH (P- CFTAH) is designed with one motor and one rotating assembly supported by a hydrodynamic bearing; it is valveless and sensorless and has the ability to produce pulsatile flow, self-balance left and right circulation without electronic intervention, and control speed automatically. Chronic animal experiments of the adult CFTAH have demonstrated stable hemodynamics and good biocompatibility for 3 months. It was possible to reduce the size of this CFTAH to 30% smaller in diameter (3.5 cm) and 30% shorter in the length (4.8 cm) with 1/3 of the total device volume, such that it can be implanted in the chest of most infants whose BSA is ≥ 0.3 m2. The pump flow range of 1.5-4.5 L/min will support patients weighing up to 50 kg (the average weight of 14- year-old children). For destination therapy, when the patient grows beyond the requirement of 4.5 L/min, the P-CFTAH can be replaced by the adult CFTAH, by disconnecting the inflow and outflow ports of the P-CFTAH from their respective inflow cuffs and outflow grafts and connecting a new adult CFTAH under cardiopulmonary bypass. The Specific Aims to achieve this goal are: (1) Refine our initial P-CFTAH prototype device for hydraulic performance and biocompatibility by using validated computational fluid dynamics analysis, and include new manufacturing improvements, which are also being applied to the adult CFTAH, (2) Perform intraoperative fitting studies to confirm the smallest patient size and critical dimensions to determine fitting requirements, (3) Perform in vitro system characterization, hemolysis testing, and endurance testing to verify that the P-CFTAH meets requirements for system performance, and (4) Perform acute and chronic in vivo experiments to validate hemodynamic response, the self-regulating mechanical design, system performance, and biocompatibility. The successful completion of this program will demonstrate the feasibility of this approach applied to a P-CFTAH and ultimately provide clinicians and pediatric patients with a valuable treatment option for heart failure.