Contemporary centrifugal continuous-flow left ventricular assist devices (LVADs) incorporate dynamic speed modulation algorithms. Hemocompatibility of these periodic unsteady pump operating conditions has been only partially explored. We evaluated whether speed modulation induces flow alterations associated with detrimental prothrombotic effects. For this aim, we evaluated the thrombogenic profile of the Heart-Ware ventricular assist device (HVAD) Lavare Cycle (LC) and HeartMate3 (HM3) artificial pulse (AP) via comprehensive numerical evaluation of (i) pump washout, (ii) stagnation zones, (iii) shear stress regimens, and (iv) modeling of platelet activation status via the platelet activity state (PAS) model. Data were compared between different simulated operating scenarios, including: (i) constant rotational speed and pump pressure head, used as reference; (ii) unsteady pump pressure head as induced by cardiac pulsatility; and (iii) unsteady rotor speed modulation of the LC (HVAD) and AP (HM3). Our results show that pump washout did not improve across the different simulated scenarios in neither the HVAD nor the HM3. The LC reduced but did not eliminate flow stagnation (-57%) and did not impact metrics of HVAD platelet activation (median PAS: +0.4%). The AP reduced HM3 flow stagnation by up to 91% but increased prothrombotic shear stress and simulated platelet activation (median PAS: +124%). Our study advances understanding of the pathogenesis of LVAD thrombosis, suggesting mechanistic implications of rotor speed modulation. Our data provide rationale criteria for the future design optimization of next generation LVADs to further reduce hemocompatibility-related adverse events.

While earlier studies reported no relevant effect of the HeartMate 3 (HM3) artificial pulse (AP) on bulk pump washout, its effect on regions with prolonged residence times remains unexplored. Using numerical simulations, we compared pump washout in the HM3 with and without AP with a focus on the clearance of the last 5% of the pump volume. Results were examined in terms of flush-volume (Vf, number of times the pump was flushed with new blood) to probe the effect of the AP independent of changing flow rate. Irrespective of the flow condition, the HM3 washout scaled linearly with flush volume up to 70% washout and slowed down for the last 30%. Flush volumes needed to washout 95% of the pump were comparable with and without the AP (1.3–1.4 Vf), while 99% washout required 2.1–2.2 Vf with the AP vs. 2.5 Vf without the AP. The AP enhanced washout of the bend relief and near-wall regions. It also transiently shifted or eliminated stagnation regions and led to rapid wall shear stress fluctuations below the rotor and in the secondary flow path. Our results suggest potential benefits of the AP for clearance of fluid regions that might elicit in-pump thrombosis and provide possible mechanistic rationale behind clinical data showing very low rate of in-pump thrombosis with the HM3. Further optimization of the AP sequence is warranted to balance washout efficacy while limiting blood damage.

The clinical management of several neurological disorders benefits from the assessment of intracranial pressure and craniospinal compliance. However, the associated procedures are invasive in nature. Here, we aimed to assess whether naturally occurring periodic changes in the dielectric properties of the head could serve as the basis for deriving surrogates of craniospinal compliance noninvasively. Methods: We designed a device and electrodes for noninvasive measurement of periodic changes of the dielectric properties of the human head. We characterized the properties of the device-electrode-head system by measurements on healthy volunteers, by computational modeling, and by electromechanical modeling. We then performed hyperventilation testing to assess whether the measured signal is of intracranial origin. Results: Signals obtained with the device on volunteers showed characteristic cardiac and respiratory modulations. Signal oscillations can be attributed primarily to changes in resistive properties of the head during cardiac and respiratory cycles. Reduction of end-tidal CO2, through hyperventilation, resulted in a decrease in the signal amplitude associated with cardiovascular action. Conclusion: Given the higher CO2 reactivity of intracranial vessels compared to extracranial ones, the results of hyperventilation testing suggest that the acquired signal is, in part, of intracranial origin. Significance: If confirmed in larger cohorts, our observations suggest that noninvasive capacitive acquisition of changes in the dielectric properties of the head could be used to derive surrogates of craniospinal compliance.

Objective. Craniospinal compliance (CC) is an important metric for the characterization of space-occupying neurological pathologies. CC is obtained using invasive procedures that carry risks for the patients. Therefore, noninvasive methods for acquiring surrogates of CC have been proposed, most recently based on changes in the head’s dielectric properties during the cardiac cycle. Here, we have tested whether changes in body position, which are known to influence CC, are reflected in a capacitively acquired signal (hereinafter referred to as W) originating from dynamic changes of the head’s dielectric properties. &#xD;Approach. Eighteen young healthy volunteers were included in the study. After 10 minutes in supine position, subjects were tilted head-up (HUT), back to 0° (horizontal, control), and then head-down (HDT). Metrics related to cardiovascular action were extracted from W, including AMP, the peak-to-valley amplitude of the cardiac modulation of W. Computational electromagnetic simulations were performed to probe the association between intracranial volume change and W. &#xD;Main results. AMP decreased during HUT (0°: 2869±597 arbitrary units (au); +75°: 2307±490 au, P=0.002) and increased during HDT (-30°: 4403±1428 au, P<0.0001). The same behavior was predicted by the electromagnetic model. &#xD;Significance. Tilting affects the distribution of CC between cranial and spinal compartments. Cardiovascular action induces compliance-dependent oscillatory changes in the intracranial fluid composition, which causes corresponding variations in the head’s dielectric properties. These manifest as increasing AMP with decreasing intracranial compliance, which suggests that W may contain information related to CC, and that it might be possible to derive CC surrogates therefrom.