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In preclinical examinations, rotodynamic blood pumps (RBPs) are predominantly evaluated at design-point conditions. In clinical practice, however, they run at diversified modes of operation. This study aimed at extending current preclinical evaluation of hemolytic profiles in RBPs toward broader, clinically relevant ranges of operation.Two implantable RBPs - the HeartMate 3 (HM3) and the HeartWare Ventricular Assist Device (HVAD) - were analyzed at three pump speeds (HM3: 4300, 5600, 7000 rpm; HVAD: 1800, 2760, 3600 rpm) with three flow rates (1-9L/min) per speed setting. Hemolysis measurements were performed in heparinized bovine blood. The delta free hemoglobin (dfHb) and the normalized index of hemolysis (NIH) served as hemolytic measures. Statistical analysis was performed by multiple comparison of the 9 operating conditions. Moreover, computational fluid dynamics (CFD) was applied to provide mechanistic insights into the interrelation between hydraulics and hemolysis by correlating numerically computed hydraulic losses with in-vitro hemolytic measures.In both devices, dfHb increased toward increasing speeds, particularly during low but also during high flow condition. By contrast, in both RBPs magnitudes of NIH were significantly elevated during low flow operation compared to high flow conditions (p0.0036). Maps of hemolytic metrics revealed morphologically similar trends to in-silico hydraulic losses (r0.793).While off-design operation is associated with increased hemolytic profiles, the setting of different operating conditions render a preclinical prediction of clinical impact with current hemolysis metrics difficult.The identified increase in hemolytic measures during episodes of off-design operation is highlighting the need to consider worst-case operation during preclinical examinations.

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.

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.

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.

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.

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.

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

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.

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.

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.

Goal: Rotary blood pumps (RBPs) typically support the left ventricle by pumping blood from the ventricle to the aorta, partially bypassing the aortic valve (AV). Monitoring the AV opening during RBP support would provide important information about cardiac–pump interaction. However, currently this information is not continuously available. In this study, an algorithm to determine AV opening using available pump signals was evaluated in humans. Methods: Pump speed changes were performed in 15 RBP patients to elicit opening of the AV. Simultaneously to pump data recordings, the AV was continuously monitored using echocardiography. The algorithm, which classifies the AV state utilizing three features (skewness, kurtosis, and crest factor) calculated from the pump flow waveform, was compared to echocardiography by using cross-validation analysis. Additionally, numerical simulation was used to evaluate effects of different pump characteristics and cannula length, as well as mitral valve insufficiency on the AV opening detection method. Results: More than 7000 heart beats were analyzed. The correct classification rate using the developed algorithm was 91.1% (sensitivity 91.0%, specificity 91.2%). Numerical simulations showed that the flow waveform shape used for AV opening detection is preserved under the different conditions studied. Conclusion: This study demonstrates that the AV opening can be reliably detected in RBP patients using available pump data. Significance: Once implemented in RBP controllers, this method will provide a novel tool to improve the management of RBP patients, particularly for adjustments of the pump speed and flow and for the evaluation of the assisted cardiac function.

Objectives Continuous flow left ventricular assist devices are used in end-stage systolic heart failure. However, about one half of the patients with heart failure exhibit diastolic dysfunction with a normal ejection fraction. In the present study, the possible hemodynamic consequences of continuous flow left ventricular assist devices use for these patients were investigated. Methods A previously developed cardiovascular model was modified to reproduce the peculiar hemodynamics of heart failure with a normal ejection fraction. The model was based on and validated with patient data derived from the published data. A continuous flow left ventricular assist device model was included and the hemodynamic effects of pump support evaluated at rest and during exercise. Results The model accurately reproduced the published data both at rest and during exercise, leading to simulated hemodynamic values within the standard deviations of patient variability. At rest, pump support decreased the end-diastolic left ventricular pressure (6 vs 15 mm Hg) and volume (88 vs 135 mL). During exercise, maximal pump support substantially unloaded the left ventricle (end-diastolic pressure, 14 vs 35 mm Hg; volume, 133 vs 158 mL) and the pulmonary venous circulation (left atrial pressure, 12 vs 24 mm Hg) and resulted in a slight increase in cardiac output (11.7 vs 9.9 L/min). Conclusions The simulation results suggested that continuous flow left ventricular assist devices improve the hemodynamics in patients with heart failure and a normal ejection fraction. For an optimal use of continuous flow left ventricular assist devices, low speeds should be maintained at rest, to avoid suction. However, during physical activity, higher speeds are needed to prevent an abnormal increase in the ventricular filling pressures typical of patients with heart failure and a normal ejection fraction.

Background Interruption of cardiopulmonary resuscitation (CPR) impairs the perfusion of the fibrillating heart, worsening the chance for successful defibrillation. Therefore ECG-analysis during ongoing chest compression could provide a considerable progress in comparison with standard analysis techniques working only during "hands-off" intervals. Methods For the reduction of CPR-related artifacts in ventricular fibrillation ECG we use a localized version of the coherent line removal algorithm developed by Sintes and Schutz. This method can be used for removal of periodic signals with sufficiently coupled harmonics, and can be adapted to specific situations by optimal choice of its parameters (e.g., the number of harmonics considered for analysis and reconstruction). Our testing was done with 14 different human ventricular fibrillation (VF) ECGs, whose fibrillation band lies in a frequency range of [1 Hz, 5 Hz]. The VF-ECGs were mixed with 12 different ECG-CPR-artifacts recorded in an animal experiment during asystole. The length of each of the ECG-data was chosen to be 20 sec, and testing was done for all 168 = 14 × 12 pairs of data. VF-to-CPR ratio was chosen as -20 dB, -15 dB, -10 dB, -5 dB, 0 dB, 5 dB and 10 dB. Here -20 dB corresponds to the highest level of CPR-artifacts. Results For non-optimized coherent line removal based on signals with a VF-to-CPR ratio of -20 dB, -15 dB, -10 dB, -5 dB and 0 dB, the signal-to-noise gains (SNR-gains) were 9.3 ± 2.4 dB, 9.4 ± 2.4 dB, 9.5 ± 2.5 dB, 9.3 ± 2.5 dB and 8.0 ± 2.7 (mean ± std, n = 168), respectively. Characteristically, an original VF-to-CPR ratio of -10 dB, corresponds to a variance ratio var(VF):var(CPR) = 1:10. An improvement by 9.5 dB results in a restored VF-to-CPR ratio of -0.5 dB, corresponding to a variance ratio var(VF):var(CPR) = 1:1.1, the variance of the CPR in the signal being reduced by a factor of 8.9. Discussion The localized coherent line removal algorithm uses the information of a single ECG channel. In contrast to multi-channel algorithms, no additional information such as thorax impedance, blood pressure, or pressure exerted on the sternum during CPR is required. Predictors of defibrillation success such as mean and median frequency of VF-ECGs containing CPR-artifacts are prone to being governed by the harmonics of the artifacts. Reduction of CPR-artifacts is therefore necessary for determining reliable values for estimators of defibrillation success. Conclusions The localized coherent line removal algorithm reduces CPR-artifacts in VF-ECG, but does not eliminate them. Our SNR-improvements are in the same range as offered by multichannel methods of Rheinberger et al., Husoy et al. and Aase et al. The latter two authors dealt with different ventricular rhythms (VF and VT), whereas here we dealt with VF, only. Additional developments are necessary before the algorithm can be tested in real CPR situations.