Development of a Small, Durable, Hemocompatible Centrifugal Blood Pump for Children

PROJECT SUMMARY Pediatric ventricular assist devices (VADs) are urgently needed to support children with heart failure awaiting transplant, especially given the scarcity of donor hearts and the complications associated with congenital heart disease. Currently, no VADs are approved for long-term use in the U.S. for children weighing approximately 10–35 kg. The immediate goal of this research is to test and refine a small and durable centrifugal blood pump (named PSU Child VAD) that we recently developed for use in children approximately 10-35 kg (BSA 0.5-1.2 m2, 1-11 years of age, and mean cardiac output of 1.5-3.5 LPM) with the weight variation of ~±1kg for 1 year old and ~±10kg for 11 year old based on growth charts developed by the Centers for Disease Control and Prevention (CDC). The device will be equipped with the optional near-physiologic pulsatility. A chronic in-vivo study was conducted on a lamb for 26 days elective, demonstrating promising biocompatibility with no evidence of end-organ failure. The goal will be achieved by three complementary, but independent aims; Aim 1) to test the prototype (Rev 0.0) PSU Child VAD through a series of 30-day in-vivo studies to validate the design and determine if the system meets the design requirements. We hypothesize that the in-vivo studies with PSU Child VAD will result in hemo-/biocompatible outcomes in terms of minimal blood trauma and no end- organ failure; Aim 2) to refine the design of PSU Child VAD (Rev 1.0, 2.0) based on the outcomes from in- silico, in-vitro, and in-vivo studies by following the FDA Design Controls approach. We hypothesize that the FDA Design Control Approach-based design iteration will result in superior hydraulic efficiency and hemo- /biocompatibility. This design is expected to minimize the occurrence of thrombosis, von Willebrand factor degradation, and hemolysis while maximizing hydraulic efficiency.; Aim 3) to develop a controller capable of providing synchronous co-pulsation to provide physiologic pulse pressures. The rationale in Aim 3 is that continuous flow blood pumps operating at a fixed speed cause static, non-physiologic pressure waveforms, which is known to cause physiologic dysfunction, such as gastrointestinal bleeding, reduced baroreflex response, and destruction of von Willebrand factor (vWF). We hypothesize that the controller will be capable of modulating the pump speed to provide physiologic arterial pulse pressure, thus balancing the physiologic levels of vWF. The proposed work is innovative because it is specifically designed to provide long-term (bridge-to-transplantation, BTT) cardiac support that fits the complex anatomy of children while also accommodating their somatic growth. This is significant because it can lead to hospital discharge and avoid the need for multiple surgeries. The long-term goal of this research is to develop a fully implantable system with the ultimate aim of enhancing the survival and quality of life for children in BTT. If successful, the device will directly benefit children awaiting donor hearts by significantly enhancing both their chances of survival and overall quality of life.