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Inspired Therapeutics (Merritt Island, FL) is developing a mechanical circulatory support (MCS) system designed as a single driver with interchangeable, extracorporeal, magnetically levitated pumps. The NeoMate system design features an integrated centrifugal rotary pump, motor, and controller that will be housed in a single compact unit. Conceptually, the primary innovation of this technology will be the combination of disposable, low-cost pumps for use with a single, multi-functional, universal controller to support multiple pediatric cardiopulmonary indications. In response to the paucity of clinically available pediatric devices, Inspired Therapeutics is specifically targeting the underserved neonate and infant heart failure (HF) patient population first. In this article, we present the development of the prototype Inspired Therapeutics NeoMate System for pediatric left ventricular assist device (LVAD) support, and feasibility testing in static mock flow loops (H-Q curves), dynamic mock flow loops (hemodynamics), and in an acute healthy ovine model (hemodynamics and clinical applicability). The resultant hydrodynamic and hemodynamic data demonstrated the ability of this prototype pediatric LVAD and universal controller to function over a range of rotary pump speeds (500–6000 RPM), to provide pump flow rates of up to 2.6 L/min, and to volume unload the left ventricle in acute animals. Key engineering challenges observed and proposed solutions for the next design iteration are also presented.

Thrombosis and bleeding are devastating adverse events in patients supported with blood-contacting medical devices (BCMDs). In this study, we delineated that high non-physiological shear stress (NPSS) caused platelet dysfunction that may contribute to both thrombosis and bleeding. Human blood was subjected to NPSS with short exposure time. Levels of platelet surface GPIbα and GPVI receptors as well as activation level of GPIIb/IIIa in NPSS-sheared blood were examined with flow cytometry. Adhesion of sheared platelets on fibrinogen, von Willibrand factor (VWF), and collagen was quantified with fluorescent microscopy. Ristocetin- and collagen-induced platelet aggregation was characterized by aggregometry. NPSS activated platelets in a shear and exposure time-dependent manner. The number of activated platelets increased with increasing levels of NPSS and exposure time, which corresponded well with increased adhesion of sheared platelets on fibrinogen. Concurrently, NPSS caused shedding of GPIbα and GPVI in a manner dependent on shear and exposure time. The loss of intact GPIbα and GPVI increased with increasing levels of NPSS and exposure time. The number of platelets adhered on VWF and collagen decreased with increasing levels of NPSS and exposure time, respectively. The decrease in the number of platelets adhered on VWF and collagen corresponded well with the loss in GPIbα and GPVI on platelet surface. Both ristocetin- and collagen-induced platelet aggregation in sheared blood decreased with increasing levels of NPSS and exposure time. The study clearly demonstrated that high NPSS causes simultaneous platelet activation and receptor shedding, resulting in a paradoxical effect on platelet function via two distinct mechanisms. The results from the study suggested that the NPSS could induce the concurrent propensity for both thrombosis and bleeding in patients.

Experiments were performed to test the hypothesis that viscoelastic properties of the swine myocardium are independent of heart rate (HR), preload (PL), and afterload (AL). Left ventricular pressure and aortic flow (AoF) waveforms were recorded in 13 swine. At different paced heart rates, an inferior vena caval occlusion (IVC) was used to reduce PL, then the IVC was released and simultaneously the aorta was clamped to increase AL. Equivalent left ventricular pressure waveform pairs consisting of an ejecting waveform (denoted as LVP) and isovolumic waveform (denoted as hydromotive pressure, HMP) were selected according to specified criteria resulting in 371 equivalent waveform pairs. From the selected waveform pairs and corresponding aortic flow waveforms, the viscoelastic properties (k and ε1) were estimated by HMP = LVP + ε1 VEJ + k × LVP × AoF. Here ε1 is the parallel elastance, k is the myocardial friction, and VEJ is the integral of AoF over ejection. Next, using k, ε1, LVP, and AoF waveforms, HMP was estimated using the equation above. To validate the model, the measured HMP and model-calculated HMP were compared for 371 matched waveform pairs (R2 = 0.97, SEE = 3.7 mmHg). The viscoelastic parameters (k and ε1) did not exhibit any clear or predictable dependence on HR, PL, and AL. [ABSTRACT FROM AUTHOR]

In the US, the most significant morbidity and mortality associated with non-valvular atrial fibrillation (NVAF) is embolic stroke, with 90% of thrombus originating from the left atrial appendage (LAA). Anticoagulation is the preferred treatment for the prevention of stroke in NVAF patients, but clinical studies have demonstrated high levels of non-compliance and increased risk of bleeding or ineligibility for anticoagulation therapy, especially in the elderly population where the incidence of NVAF is highest. Alternatively, stroke may be preventing using clinically approved surgical and catheter-based devices to exclude or occlude the LAA, but these devices continue to be plagued by peri-device leaks and thrombus formation because of residual volume. To overcome these limitations, Cor Habere (Louisville, KY) and the University of Louisville are developing a LAA closure device (StrokeShield) that completely occludes and collapses the LAA to minimize the risk of stroke. The StrokeShield device is a collapsible occluder (nitinol reinforced membrane) that completely covers the LAA orifice with an expandable conical coil anchor that attaches to the myocardium. The device is designed for catheter-based delivery and expands to completely occlude the LAA orifice and collapse the LAA. The primary advantages of the StrokeShield system are a completely sealed LAA (no peri-device flow or residual space) and smooth endothelialized connection to the left atrial wall with minimal risk of cardiac bleeding and tamponade. We tested proof-of-concept of a prototype StrokeShield device in acute (n = 2) and chronic 60-day (n = 2) healthy canine models. Acute results demonstrated that the conical coil securely attached to the myocardium (5N pull-out force) and the Nitinol umbrella fully deployed and covered the LAA ostium. Results from the chronic implants demonstrated long-term feasibility of device placement with no procedural or device-related intra- or post-operative complications, secure placement and correct positioning of the device with no device migration. The device successfully occluded the LAA ostium and collapsed the LAA with no interference with the mitral valve, circumflex coronary artery, or pulmonary veins. Necropsy demonstrated no gross signs of thrombus or end-organ damage and the device was encapsulated in the LAA. Histology demonstrated mature neointima covering the device with expected foreign body inflammatory response. These early positive results will help to guide the iterative design process for the continued development of the StrokeShield system.