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Conventional mock circulatory loops (MCLs) cannot replicate realistic hemodynamic conditions without inducing blood trauma. This constrains in-vitro hemocompatibility examinations of blood pumps to static operating conditions that do not reflect clinical scenarios. This study aimed at developing an atraumatic MCL based on a hardware-in-the-loop concept (H-MCL) that enables hemocompatibility assessment under realistic hemodynamic conditions. The atraumatic H-MCL was designed for 450±50 ml of blood with the sole blood-contacting components being the polycarbonate reservoirs, the silicone/polyvinyl-chloride tubing and the blood pump under investigation. To account for inherent coupling effects a decoupling pressure control was derived by feedback linearization, whereas the level control was addressed by an optimization task to overcome periodic loss of controllability. The HeartMate 3 was showcased to evaluate the H-MCL’s accuracy at typical hemodynamic conditions and to demonstrate the H-MCL’s atraumatic properties. Pilot hemolysis experiments were conducted with bovine (n=2) and human (n=2) blood, and evaluated in terms of the normalized index of hemolysis (NIH). Typical hemodynamic scenarios of patients with full and partial support were replicated with marginal coupling effects and root mean square error (RMSE) of 1.74±1.37 mmHg and 0.94±0.83 mmHg, respectively, while the fluid level did not exceed a range of ±4% of its target value. The initial examinations of hemolysis demonstrated the atraumatic characteristics of the novel H-MCL, as evidenced by levels of NIH (bovine: 5.1-7.2mg/100L; human: 1.6-1.8mg/100L) that are consistent with those reported in existing literature. Collectively, these findings indicated the H-MCL’s potential for in-vitro hemocompatibiltiy assessment of blood pumps within realistic hemodynamic conditions.

The ShuttlePump is a novel implantable total artificial heart (TAH) concept based on a Linear-Rotary Actuator (LiRA) and currently under development at the Power Electronic Systems Laboratory, ETH Zurich in close partnership with Charit´e Berlin and the Medical University of Vienna. This paper presents the analysis, design and realization of the ShuttlePump Linear Actuator (LA) part, which is necessary to provide about 45 N of axial actuation force. Design criteria are minimization of volume and generated power losses in the winding, which could result in excess heating and/or blood damage, i.e. protein denaturation and aggregation. The LA is implemented as a Tubular LA (TLA) to maximize the active area for linear/axial force generation. After a preliminary analysis based on first principles, the TLA is optimized in detail with the aid of FEM simulations. The experimental measurements conducted on the realized TLA prototype verify the FEM simulation results and confirm the suitability for the realization of the ShuttlePump TAH.

Objective: Total artificial hearts (TAH) are used as a temporary treatment for severe biventricular heart failure. Long-term cardiac replacement is hampered by limited durability and complication rates, which may be attributable to the modus operandi of state-of-the-art pumping systems. The aim of this study was to assess the feasibility of a novel valveless pumping principle for a durable pulsatile TAH (ShuttlePump). Methods: With a rotating and linearly shuttling piston within a cylindrical housing with 2 in- and outlets, the pump features only one single moving part and delivers pulsatile flow to both systemic and pulmonary circulation. The pump and actuation system were designed iteratively based on analytical and in silico methods, utilizing finite element methods (FEM) and computational fluid dynamics (CFD) Pump characteristics were evaluated experimentally in a mock circulation loop mimicking the cardiovascular system, while hemocompatibility related parameters were calculated numerically. Results: Pump characteristics cover the entire required operating range for a TAH (2.5 - 9L/min at 50 - 160mmHg arterial pressures) at stroke frequencies of 1.5 - 5Hz while balancing left and right atrial pressures. FEM analysis showed a mean overall copper losses of 8.84W, resulting in local blood temperature rise of < 2k. The CFD results of normalized index of hemolysis was 3.57 mg/100L and 95% of the pumps blood volume was exchanged after 1.42s. Conclusion: This study indicates feasibility of a novel pumping system for a TAH with numerical and experimental results substantiating further development of the ShuttlePump.

Background The palliation of patients with single ventricle (SV) undergoing Fontan procedure led to improved long-term survival but is still limited due to cardiovascular complications. The aim of this study was to describe the somatic and cardiovascular development of Fontan patients until adolescence and to identify determining factors. Methods We retrospectively assessed somatic growth, vascular growth of pulmonary arteries, and cardiac growth of the SV and systemic semilunar valve from 0 to 16 years of age using transthoracic echocardiography. The Doppler inflow pattern of the atrioventricular valve was quantified by E-, A-wave and E/A ratio. All data were converted to z-scores and analyzed using linear mixed effect models to identify associations with age at Fontan procedure, gender, and ventricular morphology. Results 134 patients undergoing Fontan procedure at a median age of 2.4 (IQR 2.12 to 2.8) years were analyzed. A catch-up of somatic growth after Fontan procedure until school age was found, with lower body height and weight z-scores in male patients and patients with systemic right ventricles. An early time of Fontan procedure was favorable for somatic growth, but not for vascular growth. Cardiac development indicated a decrease of SV end-diastolic diameter z-score until adolescence. Despite a trend towards normalization, E-wave and E/A ratio z-scores were diminished over the entire period. Conclusions There is a catch-up growth of somatic, vascular and cardiac parameters after Fontan procedure, which in our cohort depends on the time of Fontan procedure, ventricular morphology, and gender. Beside other factors, diastolic function of the SV remains altered.

OBJECTIVES The primary objective was to determine the impact of infant positioning on cardiopulmonary resuscitation performance during simulated pediatric cardiac arrest. DESIGN A single-center, prospective, randomized, unblinded manikin study. SETTING Medical university-affiliated simulation facility. SUBJECTS Fifty-two first-line professional rescuers (n = 52). INTERVENTIONS Performance of cardiopulmonary resuscitation was determined using an infant manikin model in three different positions (on a table [T], on the provider's forearm with the manikin's head close to the provider's elbow [P], and on the provider's forearm with the manikin's head close to the provider's palm [D]). For the measurement of important cardiopulmonary resuscitation performance variables, a commercially available infant simulator was modified. In a randomized sequence, healthcare professionals performed single-rescuer cardiopulmonary resuscitation for 3 minutes in each position. Performances of chest compression (primary outcome), ventilation, and hands-off time were analyzed using a multilevel regression model. MEASUREMENTS AND MAIN RESULTS Mean (± SD) compression depth significantly differed between table and the other two manikin positions (31 ± 2 [T], 29 ± 3 [P], and 29 ± 3 mm [D]; overall p < 0.001; repeated measures design adjusted difference: T vs P, -2 mm [95% CI, -2 to -1 mm]; T vs D, -1 mm [95% CI, -2 to -1 mm]). Secondary outcome variables showed no significant differences. CONCLUSIONS Compressions were significantly deeper in the table group compared to positions on the forearm during cardiopulmonary resuscitation, yet the differences were small and perhaps not clinically important.

The use of polytetrafluoroethylene (PTFE) material as a protective cover for left ventricular assist device (LVAD) outflow grafts (OG) is a common practice. However, it has descriptively been linked to the development of blood flow obstruction (BFO).Patient data from 194 consecutive HVAD (Medtronic Inc; Medtronic, Minneapolis, MN) recipients implanted between March 2006 and January 2021 were retrospectively analyzed. PTFE covers were used in 102 patients. Study outcomes included the incidence of BFO and survival on LVAD support.Thirty-seven patients (19.1%) developed BFO during the study period. On a multivariable Cox regression analysis, PTFE use was an independent predictor for the development of BFO (HR 2.15, 95% CI 1.03-4.48, p = .04). BFO comprised of 2 types of device malfunction: eleven patients (5.7%) developed outflow graft stenosis (OGS), and 31 patients (16.0%) developed pump thrombosis (PT). There was a significantly higher cumulative incidence of OGS in patients with PTFE cover than in those without (Gray's test, p =.03). However, the observed higher cumulative incidence of PT in PTFE patients was non-significant (Gray's test, p =.06). In a multivariable Cox regression model, the effect of PTFE use on survival was non-significant (HR 0.95, 95% CI 0.60-1.48, p =.81), while the development of BFO was independently associated with increased mortality (HR 3.43, 95% CI 1.94-6.06, p.0001).The use of PTFE OG cover in LVAD patients is associated with an increased cumulative probability of development of BFO, the latter adversely impacting survival and is therefore, harmful.

Treatment of univentricular hearts remains restricted to palliative surgical corrections (Fontan pathway). The established Fontan circulation lacks a subpulmonary pressure source and is commonly accompanied by progressively declining hemodynamics. A novel cavopulmonary assist device (CPAD) may hold the potential for improved therapeutic management of Fontan patients by chronic restoration of biventricular equivalency. This study aimed at translating clinical objectives toward a functional CPAD with preclinical proof regarding hydraulic performance, hemocompatibility and electric power consumption. A prototype composed of hemocompatible titanium components, ceramic bearings, electric motors, and corresponding drive unit was manufactured for preclinical benchtop analysis: hydraulic performance in general and hemocompatibility characteristics in particular were analyzed in-silico (computational fluid dynamics) and validated in-vitro. The CPAD's power consumption was recorded across the entire operational range. The CPAD delivered pressure step-ups across a comprehensive operational range (0–10 L/min, 0–50 mm Hg) with electric power consumption below 1.5 W within the main operating range. In-vitro hemolysis experiments (N = 3) indicated a normalized index of hemolysis of 3.8 ± 1.6 mg/100 L during design point operation (2500 rpm, 4 L/min). Preclinical investigations revealed the CPAD's potential for low traumatic and thrombogenic support of a heterogeneous Fontan population (pediatric and adult) with potentially accompanying secondary disorders (e.g., elevated pulmonary vascular resistance or systemic ventricular insufficiency) at distinct physical activities. The low power consumption implied adequate settings for a small, fully implantable system with transcutaneous energy transfer. The successful preclinical proof provides the rationale for acute and chronic in-vivo trials aiming at the confirmation of laboratory findings and verification of hemodynamic benefit., Seminars in Thoracic and Cardiovascular Surgery, 34 (1), ISSN:1043-0679, ISSN:1876-4665

A relation between the left ventricular assist device inflow cannula (IC) malposition and pump thrombus has been reported. This study aimed to investigate if the pump position, derived from chest X-rays in HeartMate 3 (HM3) patients, correlates with neurological dysfunction (ND), ischemic stroke (IS), hemorrhagic stroke (HS) and survival.This analysis was performed on routinely acquired X-rays of 42 patients implanted with a HM3 between 2014 and 2017. Device position was quantified in patients with and without ND from frontal and lateral X-rays characterizing the IC and pump in relation to spine, diaphragm or horizontal line. The primary end-point was freedom from stroke and survival one-year after HM3 implantation stratified by pump position.The analysis of X-rays, 33.5 (41.0) days postoperative, revealed a significant smaller IC angle of HM3 patients with ND versus no ND (0.1° ± 14.0° vs. 12.9° ± 10.1°, p = 0.005). Additionally, the IC angle in the frontal view, IS: 4.1 (20.9)° versus no IS: 13.8 (7.5)°, p = 0.004 was significantly smaller for HM3 patients with IS. Using receiver operating characteristics derived cut-off, IC angle10° provided 75% sensitivity and 100% specificity (C-statistic = 0.85) for predicting IS. Stratified by IC angle, freedom from IS at 12 months was 100% (10°) and 60% (10°) respectively (p = 0.002). No significant differences were found in any end-point between patients with and without HS. One-year survival was significantly higher in patients with IC angle10° versus10° (100% vs. 71.8%, p = 0.012).IC malposition derived from standard chest X-rays serves as a risk factor for ND, IS and worse survival in HM3 patients.

Computational fluid dynamics find widespread application in the development of rotary blood pumps (RBPs). Yet, corresponding simulations rely on shear stress computations that are afflicted with limited resolution while lacking validation. This study aimed at the experimental validation of integral hydraulic properties to analyze global shear stress resolution across the operational range of a novel RBP. Pressure head and impeller torque were numerically predicted based on Unsteady Reynolds-averaged Navier-Stokes (URANS) simulations and validated on a testbench with integrated sensor modalities (flow, pressure, and torque). Validation was performed by linear regression and Bland-Altman analysis across nine operating conditions. In power loss analysis (PLA), in silico hydraulic power losses were derived based on the validated hydraulic quantities and balanced with in silico shear-dependent dissipative power losses. Discrepancies among both terms provided a measure of in silico shear stress resolution. In silico and in vitro data correlated with low discordance in pressure (r = 0.992, RMSE = 1.02 mmHg), torque (r = 0.999, RMSE = 0.034 mNm), and hydraulic power losses (r = 0.990, RMSE = 0.015W). PLA revealed numerically predicted dissipative losses to be up to 34.4% smaller than validated computations of hydraulic losses. This study confirmed the suitability of URANS settings to predict integral hydraulic properties. However, numerical credibility was hampered by lacking resolution of shear-dependent dissipative losses.

Objective : The hydraulic properties of implantable rotary blood pumps (RBPs) determine their interaction with the cardiovascular system. A systematic comparison in this regard has not yet been performed for different clinically used RBPs. The aim of this study is to describe the hydraulic characteristics of four RBPs with a universal mathematical model and to compare their behavior under clinical operating conditions. Methods: First, static and dynamic pump properties of four RBPs (HVAD, Heartmate II, Heartmate 3, and Incor) including their peripheral components were identified in an in vitro setup; results were translated into mathematical models based on principles of turbomachinery including the low and backflow regions. Second, the four hydraulic models were compared in a numerical simulation of the cardiovascular system for full- and partial-support conditions. Results: A model structure applicable to each of the investigated RBPs was developed. Deviations between simulated and measured signals for static and dynamic properties were small (2.6 ± 0.5 mmHg, 0.38 ± 0.14 L/min, respectively). For a simulated partial support condition, flow pulsatility ranged from 4.1 (Incor) to 9.1 L/min (HVAD). Negative flow rates during diastole were observed in three out of four pumps. Conclusion: Hydraulic properties differ greatly between the investigated RBPs, with flat characteristics for the HVAD and Heartmate II and steeper curves for the Heartmate 3 and especially the Incor. Significance: Hydraulic characteristics of implantable RBPs are particularly important at lower pump flow rates if backflow is to be avoided. For further research, we provide dynamic hydraulic models of the four RBPs including their periphery.

Technological progress of left ventricular assist devices (LVADs) towards rotary blood pumps and the optimization of medical management contributed to the significant improvements in patient survival as well as LVAD support duration. Even though LVAD therapy is now well-established for end-stage heart failure patients, the long-term occurrence of adverse events (AE) such as bleeding, infection or stroke, still represent a relevant burden. An early detection of AE, before onset of major symptoms, can lead to further optimization of patient treatment and thus mitigate the burden of AE. Continuous patient monitoring facilitates identification of pathophysiological states and allows anticipation of AE to improve patient management. In this paper, methods, algorithms and possibilities for continuous patient monitoring based on LVAD data are reviewed. While experience with continuous LVAD monitoring is currently limited to a few centers worldwide, the pace of developments in this field is fast and we expect these technologies to have a global impact on the well-being of LVAD patients.

Background Mechanical circulatory support (MCS) in pediatric patients remains challenging because of small body size, limited availability of approved devices, and the variety of etiologies, including biventricular and univentricular physiologies. We report our single-center experience with MCS in pediatric patients in terms of survival and adverse events. Methods Outcome, etiologic, and demographic data of pediatric patients implanted with a long-term MCS device between 2011 and 2019 at the Medical University of Vienna were retrospectively collected and analyzed. Overall survival and freedom of treatment-related adverse events at 1 year were investigated by Kaplan–Meier analyses and stratified for circulation (biventricular vs univentricular), age group ( 6 years), and pump technology (pulsatile ventricular assist device [p-VAD] vs continuous flow pump [cf-VAD]). Results One-year survival of all 33 pediatric patients (median, 4 years; interquartile range, 0-13 years) was 73%, with a tendency toward better outcomes in patients with biventricular circulation than in those with univentricular circulation (80%; n = 25 vs 50%; n = 8; P = .063). The trends toward better survival probability in older patients and in patients with cf-VADs did not reach statistical significance (63.2% vs 85.7%; P = .165 and 82.4% vs 62.5%; P = .179, respectively). Freedom from adverse events was higher in older patients (57.1% vs 5.6%; P Conclusions MCS is a promising therapy for a broad spectrum of pediatric patients, irrespective of heart failure etiology, age, and pump type. With increasing experience, improved devices, and patient selection, MCS may become a valuable treatment option for patients with univentricular hearts.

In rotodynamic blood pumps (RBPs) a substantial proportion of input energy is dissipated into the blood. This energy may propel damaging work on blood constituents. To date, the link between this hydraulic energy dissipation and respective hemolytic action in RBPs remains vastly unknown. In this study, computational fluid dynamics is applied to compute the hydraulic energy dissipation at 9 operating conditions in two RBPs (HM3: HeartMate 3; HVAD: HeartWare Ventricular Assist Device). Respective interrelations with hemolytic pump performance are elucidated by comparing these computations with in silico predicted and in vitro measured hemolysis. Despite different pump geometries, hydraulic loss magnitudes, and distributions, global hydraulic energy dissipation shows strong correlation (r > 0.95) to in vitro hemolysis with scaling factors in the same order of magnitude for both devices (phi(HM3) = 0.599 (mL g) (J 100L)(-1); phi(HVAD) = 0.716 (mL g) (J 100L)(-1)). The analytical description of hydraulic energy dissipation reveals to be a function of shear stresses and exposure time, unmasking its analogy to the power-law formulation of hemolysis. This hydraulics-based analysis may denote a step ahead to relate turbomachinery to bioengineering and may provide mechanistic insights into the relation between RBP design, hydraulic properties, and hemolytic performance., Advanced Theory and Simulations, 5 (9)

OBJECTIVESWe reviewed our institutional experience with outflow graft stenosis (OGS) in 3 contemporary left ventricular assist devices (LVAD).METHODSData from 347 consecutive adult recipients of LVAD [Medtronic HVAD (n = 184, 53.0%), Abbott HeartMate II (n = 62, 17.9%) and Abbott HeartMate 3 (n = 101, 29.1%)] implanted between March 2006 and October 2019 were analysed retrospectively. Primary study end points were the incidence of OGS necessitating treatment and survival on LVAD support.RESULTSDuring the study period, 17 patients (4.9%) developed OGS requiring treatment with a probability of 0.6% at 1 year, 1.9% at 2 years, 3.8% at 3 years, 4.7% at 4 years and 5.9% at 5 years of LVAD support. Notably, in 13.8% of patients, a compression-related narrowing of the outflow graft with a probability of 1.5% at 6 months, 1.8% 1 year, 6.0% at 2 years, 12.3% at 3 years, 15.4% at 4 years and 16.6% at 5 years of LVAD support with no difference between devices (P = 0.26) was observed. There was a trend towards increased risk of mortality with OGS (hazard ratio 2.21, 95% confidence interval 0.87–5.51; P = 0.09). OGS preferentially occurred in segments of the outflow graft covered by a protective coating.CONCLUSIONSOGS is a rare but potentially lethal complication during LVAD support. Modifications of pump design and implant techniques may be needed because OGS preferentially occurs within covered portions of the outflow graft. Systematic screening may be warranted.

The considerable contribution of parasitic measurement effects in fluid flow machines of small performance classes remains a major challenge in the assessment of corresponding hydraulic characteristics such as hydraulic losses and efficiencies. However, a standardized experimental approach to accurately quantify such properties is of paramount importance for the design of rotary blood pumps with low hydraulic power and torque. This study proposes a novel test bench to accurately assess hydraulic and mechanical characteristics of pumps designed for a mechanical power input of up to 20,9W, a maximum rotational speed of 7000min−1 and a maximum torque of 10mNm. Key feature of the iteratively optimized test bench is a torque measuring shaft combined with ceramic bearings and seals that minimizes the friction torque to 0.66–0.69mNm. Preliminary measurements for a double-inflow, double-outflow circulatory support pump with maximum torque of 1.71mNm and hydraulic power of 0.15W, demonstrated both the feasibility of the hydraulic and mechanical design of the test bench and the reproducibility of the measured data. These results warrant the applicability of the presented test-bench for the investigation of typical cardiac assist systems as well as for all other hydraulic flow machines of the equivalent performance class.

Treatment of heart failure with preserved ejection fraction (HFpEF) remains a major unmet medical need. An implantable valveless pulsatile pump with a single cannula—the CoPulse pump—may provide beneficial hemodynamic support for select HFpEF patients when connected to the failing ventricle. We aimed to demonstrate hemodynamic efficacy and hemocompatible design feasibility for this novel assist device. The hemodynamic effect of the pump was investigated with an in vitro circulatory mock loop and an ex vivo isolated porcine heart model. The hydraulic design was optimized using computational fluid dynamics (CFD), and validated by 4D-flow magnetic resonance imaging (MRI). The pump reduced left atrial pressure (> 27%) and increased cardiac output (> 14%) in vitro. Ex vivo experiments revealed elevated total stroke volume at increased end-systolic volume during pump support. Asymmetric cannula positioning indicated superior washout, decreased stagnation (8.06 mm2 vs. 31.42 mm2), and marginal blood trauma potential with moderate shear stresses ( 0.76). The CoPulse pump proved hemodynamically effective. Hemocompatibility metrics were comparable to those of a previously reported, typical pulsatile pump with two cannulae. The encouraging in vitro, ex vivo, and hemocompatibility results substantiate further development of the CoPulse pump., Annals of Biomedical Engineering, 48, ISSN:1573-9686, ISSN:0191-5649, ISSN:0090-6964

The aim of this work was the development of an isolated heart setup to delineate the interactions between intraventricular flow features, hemodynamic parameters and mechano-energetics after certain mitral valve therapies. Five porcine hearts were explanted and prepared for (i) edge-to-edge mitral valve repair, (ii) implantation of a rotatable biscupid mechanical valve prosthesis. Flow structures were visualized using echocardiography while hemodynamics was recorded in terms of pressures, flow rates and ventricular volume. Hemodynamic and cardiac mechano-energetics implied a marginal effect (

Investigations of ventricular flow patterns during mechanical circulatory support are limited to in vitro flow models or in silico simulations, which cannot fully replicate the complex anatomy and contraction of the heart. Therefore, the feasibility of using echocardiographic particle image velocimetry (Echo-PIV) was evaluated in an isolated working heart setup. Porcine hearts were connected to an isolated, working heart setup and a left ventricular assist device (LVAD) was implanted. During different levels of LVAD support (unsupported, partial support, full support), microbubbles were injected and echocardiographic images were acquired. Iterative PIV algorithms were applied to calculate flow fields. The isolated heart setup allowed different hemodynamic situations. In the unsupported heart, diastolic intra-ventricular blood flow was redirected at the heart’s apex towards the left ventricular outflow tract (LVOT). With increasing pump speed, large vortex formation was suppressed, and blood flow from the mitral valve directly entered the pump cannula. The maximum velocities in the LVOT were significantly reduced with increasing support. For the first time, cardiac blood flow patterns during LVAD support were visualized and quantified in an ex vivo model using Echo-PIV. The results reveal potential regions of stagnation in the LVOT and, in future the methods might be also used in clinical routine to evaluate intraventricular flow fields during LVAD support., Annals of Biomedical Engineering, 48 (2), ISSN:1573-9686, ISSN:0191-5649, ISSN:0090-6964

Ventricular assist devices (VADs), among which the HeartMate 3 (HM3) is the latest clinically approved representative, are often the therapy of choice for patients with end-stage heart failure. Despite advances in the prevention of pump thrombosis, rates of stroke and bleeding remain high. These complications are attributed to the flow field within the VAD, among other factors. One of the HM3's characteristic features is an artificial pulse that changes the rotor speed periodically by 4000 rpm, which is meant to reduce zones of recirculation and stasis. In this study, we investigated the effect of this speed modulation on the flow fields and stresses using high-resolution computational fluid dynamics. To this end, we compared Eulerian and Lagrangian features of the flow fields during constant pump operation, during operation with the artificial pulse feature, and with the effect of the residual native cardiac cycle. We observed good washout in all investigated situations, which may explain the low incidence rates of pump thrombosis. The artificial pulse had no additional benefit on scalar washout performance, but it induced rapid variations in the flow velocity and its gradients. This may be relevant for the removal of deposits in the pump. Overall, we found that viscous stresses in the HM3 were lower than in other current VADs. However, the artificial pulse substantially increased turbulence, and thereby also total stresses, which may contribute to clinically observed issues related to hemocompatibility.

The HeartWare HVAD is a radial rotary blood pump with a combination of passive magnetic and hydrodynamic bearings to levitate the impeller. The axial gap size between impeller and housing in this bearing and its sensitivity to speed, flow, and pressure difference is difficult to assess. Shear stresses are exceptionally high in this tiny gap making it important for blood damage and related adverse events. Therefore, the aim of this study was to measure the axial gap clearance in the HVAD at different operating conditions employing radiography. To quantify the gap size in the HVAD, the pump was positioned 30 mm in front of the X-ray source employing a microfocus X-ray tube with an acceleration voltage up to 300 kV. Beams were detected on a flat panel detector (Perkin Elmer XRD 1611-CP3). The pump was connected to a tubing circuit with a throttle to adjust flow (0, 5, 10 L/min) and a water glycerol mixture to set the desired viscosity (1, 4, 8 mPas). Rotational speed was varied between 1800 and 3600 rpm. In this study, for clinically relevant conditions at 5 L/min and 2700 rpm, the axial gap was 22 µm. The gap size increased with rotational speeds dependent on the viscosity (2.8, 6.9, and 9.4 µm/1000 rpm for 1, 4, and 8 mPas, respectively), but was independent from the volume flow and the pressure head at constant speeds. In summary, using X-ray radiographic imaging small gaps in a rotary blood pump during operation can be measured in a nondestructive contact-free way. The axial hydrodynamic bearing gap in the HVAD pump was determined to be in the range of about three times the diameter of a red blood cell. Its dependence on operating volume flow and generated pressure head across the pump is not pronounced.

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 HeartWare 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.

Background: Assessment of left ventricular (LV) recovery under continuous-flow LV assist device therapy is hampered by concomitant pump support. We describe derivation of noninvasive pressure-volume loops in continuous-flow LV assist device patients and demonstrate an application in the assessment of recovery. Methods and Results: Using pump controller parameters and noninvasive arterial pressure waveforms, central aortic pressure, outflow conduit pressure gradient, and instantaneous LV pressure were calculated. Instantaneous LV volumes were calculated from echocardiographic LV end-diastolic volume accounting for the integral of pump flow with respect to time and aortic ejection volume derived from the pump speed waveform. Pressure-volume loops were derived during pump speed adjustment and following bolus intravenous milrinone to assess changes in loading conditions and contractility, respectively. Fourteen patients were studied. Baseline noninvasive LV end-diastolic pressure correlated with invasive pulmonary arterial wedge pressure ( r 2 =0.57, root mean square error 5.0 mm Hg, P =0.003). Measured noninvasively, milrinone significantly increased LV ejection fraction (40.3±13.6% versus 36.8±14.2%, P P =0.006), and end-systolic elastance (1.03±0.57 versus 0.89±0.38 mm Hg/mL, P =0.008), consistent with its expected inotropic effect. Milrinone reduced myocardial oxygen consumption (0.15±0.06 versus 0.16±0.07 mL/beat, P =0.003) and improved myocardial efficiency (43.7±14.0% versus 41.2±15.5%, P =0.001). Reduced pump speed caused increased LV end-diastolic volume (190±80 versus 165±71 mL, P P =0.024), consistent with a predictable increase in preload. There was increased myocardial oxygen consumption (0.16±0.07 versus 0.14±0.06 mL O 2 /beat, P P =0.24), reflecting decreased myocardial efficiency (39.2±12.7% versus 45.2±17.0%, P =0.003). Conclusions: Pressure-volume loops are able to be derived noninvasively in patients with the HeartWare HVAD and can detect induced changes in load and contractility.

This paper presents a constrained optimization and calorimetric experimental analysis of low torque (2.2 mNm) axial flux permanent magnet motors with small active rotor surface area (1.4 cm2) with the aim to drive an implantable blood pump to support patients with a Fontan circulation. Till today, no such treatment option is clinically available, despite the urgent need. For a previously presented implantable blood pump concept, in this paper now the corresponding motors are optimized concerning efficiency and power density, where e.g. the optimal permanent magnet and back-iron height of the rotor or the optimal pole pair number and tooth height of the stator are determined. Afterwards, the different motor prototypes are realized, tested and compared to each other. Besides the implant size also the generated motor losses are very crucial, since the local temperature increase of the blood and surrounding tissue must always be kept below 2 °C. However, as will be shown in this paper, due to the fact that the low torque of the motors cannot be separated from the test-bench bearing friction with conventional torque sensors, a sophisticated calorimetric test bench to accurately measure the motor losses is needed.

During the development process of active or passive cardio-vascular implants, such as ventricular assist devices or vascular grafts, extensive in-vitro testing is required. The aim of the study was to develop a versatile hybrid mock circulation (HMC) which can support the development of such implants that have a complex interaction with the circulation. The HMC operates based on the hardware-in-the-loop concept with a hydraulic interface of four pressure-controlled reservoirs allowing the in-teraction of the implant with a numerical model of the cardi-ovascular system. Three different conditions were investigated to highlight the versatility and the efficacy of the HMC during the development of such implants: 1) biventricular assist device (BiVAD) support with progressive aortic valve insufficiency, 2) total artificial heart (TAH) support with increasing pulmonary vascular resistance, and 3) flow distribution in a total cavo-pulmonary connection (TCPC) in a Fontan circulation during exercise. Realistic pathophysiologic waveforms were generated with the HMC and all hemodynamic conditions were simulated just by adapting the software. The results of the experiments indicated the potential of physiologic control during BiVAD or TAH support to prevent suction or congestion events, which may occur during constant-speed operation. The TCPC geom-etry influenced the flow distribution between the right and the left pulmonary artery, which was 10% higher in the latter and led to higher pressures. Together with rapid prototyping meth-ods, the HMC may enhance the design of implants to achieve better hemodynamics. Validation of the models with clinical recordings is suggested for increasing the reliability of the HMC., ASAIO Journal, 65 (5), ISSN:1058-2916, ISSN:1538-943X

In rotary blood pump recipients with low blood pressure pulsatility, current oscillometric methods to measure blood pressure are not applicable. The aim of this study was to use ultrasonic Doppler flow measurements to determine blood pressure in this patient population noninvasively. In 28 rotary blood pump recipients, blood pressure was measured three times with the developed Doppler method and compared to the invasive arterial line (n = 15) or to the oscillometric Terumo Elemano BP monitor (n = 13). Blood velocities in the radial artery were recorded by the new Doppler sensor during cuff deflation. A sigmoid curve was fitted to a preprocessed velocity signal and the systolic and mean arterial pressures were determined. A total of 84 measurements were performed, and 17 recordings were visually excluded from further analysis due to obvious artifacts. Both the systolic and mean pressures derived by the Doppler method were in good accordance with the invasively measured pressure (3.7 ± 6.6 mmHg for the systolic and −2.1 ± 7.3 mmHg for the mean pressure). A good agreement between the oscillometric monitor and the Doppler method for the systolic (0.0 ± 6.0 mmHg) and mean (1.0 ± 5.9 mmHg) pressures was observed. In this study, a new Doppler blood pressure measurement system was developed and clinically validated. The novel sensor allows easier placement above the radial artery compared to commercial probes. An algorithm was developed which processes the Doppler signal robustly and is able to determine the systolic as well as the mean arterial blood pressure.

Effective treatment of patients with terminal heart failure and preserved ejection fraction (HFpEF) is an unmet medical need. The aim of this study was to investigate a novel valveless pulsatile pump as a therapeutic option for the HFpEF population through comprehensive in silico investigations. The pump was simulated in a numerical model of the cardiovascular system of four HFpEF phenotypes and compared to a typical case of heart failure with reduced ejection fraction (HFrEF). The proposed pump, which was modeled as being directly connected to the left ventricle, features a single valveless inlet and outlet cannula and is driven in co-pulsation with the left ventricle. We collected hemodynamics for two different pump volumes (30 and 60 mL). In all HFpEF conditions, the 30 mL pump improved the cardiac output by approximately 1 L/min, increased the mean arterial pressure by > 11% and lowered the mean left atrial pressure by > 30%. With the larger (60 mL) stroke volume, these hemodynamic improvements were more pronounced. In the HFrEF condition however, these effects were three times less in magnitude. In this simulation study, the valveless pulsatile device improves hemodynamics in HFpEF patients by increasing the total stroke volume. The hemodynamic benefits are achieved with a small device volume comparable to implantable rotary blood pumps.

Background: Long-term survival of patients with a single ventricle palliated with a Fontan procedure is still limited. No curative treatment options are available. To investigate the pathophysiology and potential treatment options, such as mechanical circulatory support (MCS), appropriate large animal models are required. The aim of this review was to analyze all full-text manuscripts presenting approaches for an extracardiac total cavopulmonary connection (TCPC) animal model to identify the feasibility and limitations in the acute and chronic setting. Methods: A literature search was performed for full-text publications presenting large animal models with extracardiac TCPCs on Pubmed and Embase. Out of 454 reviewed papers, 23 manuscripts fulfilled the inclusion criteria. Surgical procedures were categorized and hemodynamic changes at the transition from the biventricular to the univentricular condition analyzed. Results: Surgical procedures varied especially regarding coronary venous flow handling and anatomic shape of the TCPC. In most studies (n = 14), the main pulmonary artery was clamped and the coronary venous flow redirected by additional surgical interventions. Only in five reports, the caval veins were connected to the right pulmonary artery to create a true TCPC shape, whereas in all others (n = 18), the veins were connected to the main pulmonary artery. An elevated pulmonary vascular resistance was identified as a limiting hemodynamic factor for TCPC completion in healthy animals. Conclusions: A variety of acute TCPC animal models were successfully established with and without MCS, reflecting the most important hemodynamic features of a Fontan circulation; however, chronic animal models were not reported.

Realistic training of cardiologic interventions in a heart catheter laboratory is hardly achievable with simple tools and requires animal experiments. Therefore, first a simple mock circuit connected to a porcine heart mimicking the natural heart motion was developed. In a second step the setup was duplicated to drive both sides of the heart independently to generate motion and physiologic pressures and flows. Using this simple setup cardiologic interventions (arterial and ventricular septal defects ASD/VSD closure) were performed successfully and allowed realistic training under the C-arm, echocardiography, placement of catheters and repair of ASD/VSD. With the second setup flows of up to 4 l/min were achieved in both sides of the heart at maximum left and right ventricular pressures of 80 mm Hg and 30 mm Hg respectively. This method is inexpensive and represents a realistic alternative to training in animal experiments.

New left ventricular assist devices (LVADs) offer both important advantages and potential hazards. VAD development requires better and expeditious ways to identify these advantages and hazards. We validated in an isolated working heart the hemodynamic performance of an intraventricular LVAD and investigated how its outflow cannula interacted with the aortic valve. Hearts from six pigs were explanted and connected to an isolated working heart setup. A miniaturized LVAD was implanted within the left ventricle (tMVAD, HeartWare Inc., Miami Lakes, FL, USA). In four experiments blood was used to investigate hemodynamics under various loading conditions. In two experiments crystalloid perfusate was used, allowing visualization of the outflow cannula within the aortic valve. In all hearts the transapical miniaturized ventricular assist device (tMVAD) implantation was successful. In the blood experiments hemodynamics similar to those observed clinically were achieved. Pump speeds ranged from 9 to 22 krpm with a maximum of 7.6 L/min against a pressure difference between ventricle and aorta of ∼50 mm Hg. With crystalloid perfusate, central positioning of the outflow cannula in the aortic root was observed during full and partial support. With decreasing aortic pressures the cannula tended to drift toward the aortic root wall. The tMVAD could unload the ventricle similarly to LVADs under conventional cannulation. Aortic pressure influenced central positioning of the outflow cannula in the aortic root. The isolated heart is a simple, accessible evaluation platform unaffected by complex reactions within a whole, living animal. This platform allowed detection and visualization of potential hazards.

Objective Mechanical circulatory support has become a standard therapy for adult patients with end-stage heart failure. For pediatric patients, technologic development lags behind with no currently approved implantable rotary blood pump. As an alternative, the HeartWare Ventricular Assist Device (Medtronic, Minneapolis, Minn), originally designed for adults, is increasingly used in pediatric patients. The aim of this multicenter study was to assess in silico, in vitro, and in vivo the blood trauma potential of this pump in pediatric application. Methods Clinical outcome and indicators for in vivo blood trauma were investigated retrospectively in 14 pediatric patients with the HeartWare Ventricular Assist Device (age 11.3 ± 4.8 years). Blood trauma mechanisms of the HeartWare Ventricular Assist Device were examined in silico and in vitro at an adult and pediatric operating point (5 L/min and 2.5 L/min at 2800 rpm and 2200 rpm, respectively). The flow was simulated by computational fluid dynamics and analyzed regarding flow structures, shear stresses, and washout. Hemolysis was assessed with pumps circulating bovine blood in a temperate flow circuit. Results In the retrospective in vivo analysis, lactate dehydrogenase and D-dimer values were 1.5- and 3-fold elevated, respectively, compared with adult patients with the HeartWare Ventricular Assist Device. Major bleedings were observed in 42.9%, and suspected pump thrombosis and neurologic dysfunction were observed in 14.3% of all patients. In the pediatric conditions, simulations predicted elevated mechanical stress profile below 50 Pa, more stagnant flow field, and longer washout times within the pump. In vitro measurements revealed an increased normalized index of hemolysis (17.5 vs 8.2 mg/100 L; P = .0021). Conclusions The HeartWare Ventricular Assist Device, operated at lower speeds and flows, induces elevated blood trauma. Further studies are required to assess the clinical implications of these findings.

In patients with a single ventricle, failure of the cardiovascular system may be prevented by substituting the missing sub-pulmonary ventricle with a pump. The aim of this study was to design and evaluate a device for long-term cavopulmonary support. A radial pump with two inlets and two outlets, a single impeller, mechanical bearings, and dual motor configuration was developed. Motor and fluid dynamic components were designed and simulated using computational methods including thermal effects. Hydraulic properties were determined in-vitro with 3D-printed prototypes. The pump design was virtually implanted in an MRI-derived total cavopulmonary connection (TCPC). Computational fluid dynamics (CFD) showed flow fields without regions of flow stagnation (velocity

Purpose: Rotary blood pumps are a promising treatment approach for patients with a total cavopulmonary connection and a failing cardiovascular system. The aim of this study was to investigate the hemodynamic effects of cavopulmonary support using a numerical model with closed-loop baroreflex and exercise mechanisms. Methods: A numerical model of the univentricular cardiovascular system was developed, mimicking the hemodynamics during rest and exercise. Rotary blood pumps with different hydraulic pump characteristics (flat vs steep pressure-flow relationships) were investigated in the cavopulmonary position. Furthermore, two support modes—a constant speed setting and a physiologically controlled speed—were examined. Results: Hemodynamics without rotary blood pumps were achieved with less than 10% deviation from reported values during rest and exercise. Rotary blood pumps at constant speed improve the hemodynamics at rest, however, they constitute a hydraulic resistance during light (steep characteristics) or moderate (flat characteristics) exercise. In contrast, physiologic control increases cardiac output (moderate exercise: 8.2 vs 7.4 L/min) and reduces sympathetic activation (heart rate at moderate exercise: 111 vs 123 bpm). Conclusion: In this simulation study, the necessity of an automatically controlled rotary blood pump in the cavopulmonary position was shown. A pump at constant speed might constitute an additional resistance to venous return during physical activity. Therefore, a physiologic control algorithm based on the pressure difference between the caval veins and the atrial pressure is proposed to improve hemodynamics, especially during physical activity.

Advancements in both the design of mechanical circulatory support (MCS) and medical care for recipients have led to steady improvements in patient survival over the last decades. Indeed, current generations of ventricular assist devices (VADs), for example, provide important therapeutic alternatives for individuals with heart failure that may be ineligible for heart transplant. Nevertheless, it is clear that freedom from adverse events (including premature death) is experienced by an unacceptably low proportion of MCS recipients, as evidenced by recent INTERMACS reports.1 The primary complications observed post surgery remain neurological disorders (e.g. stroke), multi-system organ failure and infection. While infection remains an ongoing area of interest with important advancement, it is currently being explored whether a common aetiology may explain the high rate of organ failure (including the brain).

Purpose Exercise capacity is usually evaluated by peak oxygen consumption (peak-VO2). However, assessment of peak-VO2 in patients with a left ventricular assist device (LVAD) might not be the best method to provide insight into their daily life activity. The aim of this study was to assess the postoperative activity of LVAD patients using actigraphy and to compare these patients to a healthy and a heart-transplanted (HTx) population. Methods Activity was continuously monitored using wrist-accelerometers in LVAD patients after implantation, during 4 weeks of rehabilitation following hospital discharge, and at 2 follow-up assessments. Peak-VO2 values measured during rehabilitation were correlated with activity. Additionally, actigraphy data from LVAD recipients were compared with data measured in healthy and HTx subjects. Results After hospital discharge a significant increase in physical activity of LVAD recipients was observed (55 ± 28 vs. 102 ± 23 Activity Scores, n = 11, p = 0.002). During rehabilitation as well as at the follow-ups (140 ± 43 and 253 ± 33 days post-implantation) no significant increase in activity was observed. Peak-VO2 values correlated to daily activity both in LVAD and HTx patients (r > 0.5). Average daily activity was significantly lower in LVAD and HTx patients than in the healthy population (130 ± 30 and 148 ± 60 vs. 245 ± 63 Activity Score; n = 18 in each group, p < 0.001). Conclusions Activity in LVAD recipients increased substantially after hospital discharge with no further significant improvement observed during a period of 8.5 months. Similarly to the peak-VO2, also the daily activity of LVAD recipients was 53% compared to healthy subjects. These results highlight the need for an optimized physical therapy in this patient cohort.

As the aortic valve (AV) opens, the pump pressure head remains constant, which is reflected as a "notch/plateau" in pump pressure and flow signals. However, instantaneous flow estimation may be influenced by friction and is particularly difficult in axial pumps. Therefore, a new method to determine the duration of AV opening based on the area under the curve (AUC) of the power spectral density analysis of pump speed signal was developed. Data from patients implanted with HeartWare HVAD left ventricular assist device were studied at different pump speeds, with simultaneous transthoracic echocardiography in two cohorts. In the first group, pump data of 15 patients were used to investigate the ability to discriminate between an open and closed AV. In the second cohort of a further 13 patients, the duration of AV opening was measured from digitized M-mode images, and the relationship between the AV opening time and the new method assessed. In 14 of the initial 15 patients, AV status could be discriminated using only one threshold for all patients. In the second cohort, gradual speed reduction resulted in aortic valve opening in 12 of the 13 patients. The correlation between AV opening duration and AUC was 0.96 ± 0.03. Regression analysis indicated a linear relationship in each of the patients with a small error between the fit and the measured opening time (root mean square error = 11.0 ± 7.6 ms). However, the slopes (69.0 ± 52.8) and intercepts (-31.4 ± 78.0) varied widely between patients. The sensitivity and specificity for the new method using AUC threshold of 0.95 for aortic valve closure was 95% and 91%, respectively. The newly developed method to detect AV opening not only provides information on the AV status during LVAD support (open/closed) but also gives insight into the duration of AV opening. Because the slope of the relationship varies from patient to patient, initial training and adaptation of the method to each patient seems to be required.

The HeartWare HVAD is a radial rotary blood pump with a combination of passive magnetic and hydrodynamic bearings to levitate the impeller. The axial gap size between impeller and housing in this bearing and its sensitivity to speed, flow, and pressure difference is difficult to assess. Shear stresses are exceptionally high in this tiny gap making it important for blood damage and related adverse events. Therefore, the aim of this study was to measure the axial gap clearance in the HVAD at different operating conditions employing radiography. To quantify the gap size in the HVAD, the pump was positioned 30 mm in front of the X-ray source employing a microfocus X-ray tube with an acceleration voltage up to 300 kV. Beams were detected on a flat panel detector (Perkin Elmer XRD 1611-CP3). The pump was connected to a tubing circuit with a throttle to adjust flow (0, 5, 10 L/min) and a water glycerol mixture to set the desired viscosity (1, 4, 8 mPas). Rotational speed was varied between 1800 and 3600 rpm. In this study, for clinically relevant conditions at 5 L/min and 2700 rpm, the axial gap was 22 µm. The gap size increased with rotational speeds dependent on the viscosity (2.8, 6.9, and 9.4 µm/1000 rpm for 1, 4, and 8 mPas, respectively), but was independent from the volume flow and the pressure head at constant speeds. In summary, using X-ray radiographic imaging small gaps in a rotary blood pump during operation can be measured in a nondestructive contact-free way. The axial hydrodynamic bearing gap in the HVAD pump was determined to be in the range of about three times the diameter of a red blood cell. Its dependence on operating volume flow and generated pressure head across the pump is not pronounced.