An evaluation of physical and augmented patient-specific intracranial aneurysm simulators on microsurgical clipping performance and skills: a randomized controlled study.

OBJECTIVE: In the era of flow diversion, there is an increasing demand to train neurosurgeons outside the operating room in safely performing clipping of unruptured intracranial aneurysms. This study introduces a clip training simulation platform for residents and aspiring cerebrovascular neurosurgeons, with the aim to visualize peri-aneurysm anatomy and train virtual clipping applications on the matching physical aneurysm cases. METHODS: Novel, cost-efficient techniques allow the fabrication of realistic aneurysm phantom models and the additional integration of holographic augmented reality (AR) simulations. Specialists preselected suitable and unsuitable clips for each of the 5 patient-specific models, which were then used in a standardized protocol involving 9 resident participants. Participants underwent four sessions of clip applications on the models, receiving no interim training (control), a video review session (video), or a video review session and holographic clip simulation training (video + AR) between sessions 2 and 3. The study evaluated objective microsurgical skills, which included clip selection, number of clip applications, active simulation time, wrist tremor analysis during simulations, and occlusion efficacy. Aneurysm occlusions of the reference sessions were assessed by indocyanine green videoangiography, as well as conventional and photon-counting CT scans. RESULTS: A total of 180 clipping procedures were performed without technical complications. The measurements of the active simulation times showed a 39% improvement for all participants. A median of 2 clip application attempts per case was required during the final session, with significant improvement observed in experienced residents (postgraduate year 5 or 6). Wrist tremor improved by 29% overall. The objectively assessed aneurysm occlusion rate (Raymond-Roy class 1) improved from 76% to 80% overall, even reaching 93% in the extensively trained cohort (video + AR) (p = 0.046). CONCLUSIONS: The authors introduce a newly developed simulator training platform combining physical and holographic aneurysm clipping simulators. The development of exchangeable, aneurysm-comprising housings allows objective radio-anatomical evaluation through conventional and photon-counting CT scans. Measurable performance metrics serve to objectively document improvements in microsurgical skills and surgical confidence. Moreover, the different training levels enable a training program tailored to the cerebrovascular trainees' levels of experience and needs.

Effect of hot water maceration, rehydration, and soft tissue presence on 3D geometry of bone.

PURPOSE: In forensic medicine, maceration is often essential for examining bone surfaces, serving purposes such as identifying cut marks, making geometric measurements, and determining the victim's age. While hot water maceration removes soft tissue effectively, it is known to cause bone surface shrinkage. This raises the question of whether this effect is permanent or if it can be partially reversed through rehydration, considering the presence of soft tissue. METHODS: Computed tomography (CT) scans were conducted on the radii of 20 paired human anatomic forearm specimens. Subsequently, the radii were extracted, macerated in 60 °C water, CT-scanned in an air environment, rehydrated, re-implanted into the forearms, and CT-scanned again. RESULTS: Maceration resulted in a mean shrinkage of 0.12 mm on the outer bone surface. This shrinkage was nearly fully recoverable for the diaphysis after rehydration and accounting for soft tissue surrounding the bone. In contrast, the epiphysis showed permanent shrinkage, likely due to the loss of small bone fragments. Analysis of the inner bone surface indicated a smaller effect, but with significant standard deviations, especially for the epiphysis, possibly related to the less well-defined nature of the inner bone surface. CONCLUSION: The epiphyseal surface of hot water-macerated bone will, on average, be approximately 0.15 mm deflated and cannot retain the original surface. On the other hand, the diaphyseal surface is less affected and can be nearly completely restored after rehydration and accounting for soft tissue surrounding the bone.

Inflow cannula position as risk factor for stroke in patients with HeartMate 3 left ventricular assist devices.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 angle <10° 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 angle >10° versus <10° (100% vs. 71.8%, p = 0.012). CONCLUSIONS: IC malposition derived from standard chest X-rays serves as a risk factor for ND, IS and worse survival in HM3 patients.

Left ventricular assist device driveline infections in three contemporary devices.

Driveline infections (DLI) are common adverse events in left ventricular assist devices (LVADs), leading to severe complications and readmissions. The study aims to characterize risk factors for DLI readmission 2 years postimplant. This single-center study included 183 LVAD patients (43 HeartMate II [HMII], 29 HeartMate 3 [HM3], 111 HVAD) following hospital discharge between 2013 and 2017. Demographics, clinical parameters, and outcomes were retrospectively analyzed and 12.6% of patients were readmitted for DLI, 14.8% experienced DLI but were treated in the outpatient setting, and 72.7% had no DLI. Mean C-reactive protein (CRP), leukocytes and fibrinogen were higher in patients with DLI readmission (P < .02) than in outpatient DLI and patients without DLI, as early as 60 days before readmission. Freedom from DLI readmission was comparable for HMII and HVAD (98% vs. 87%; HR, 4.52; 95% CI, 0.58-35.02; P = .15) but significantly lower for HM3 (72%; HR, 10.82; 95% CI, 1.26-92.68; P = .03). DLI (HR, 1.001; 95% CI, 0.999-1.002; P = .16) or device type had no effect on mortality. DLI readmission remains a serious problem following LVAD implantation, where CRP, leukocytes, and fibrinogen might serve as risk factors already 60 days before. HM3 patients had a higher risk for DLI readmissions compared to HVAD or HMII, possibly because of device-specific driveline differences.

The impact of 3D-printed LAY-FOMM 40 and LAY-FOMM 60 on L929 cells and human oral fibroblasts.

OBJECTIVES: LAY-FOMM is a promising material for FDA-approved Fused Deposition Modeling (FDM) applications in drug delivery. Here we investigated the impact on oral cells. MATERIALS AND METHODS: We evaluated the impact of 3D-printed LAY-FOMM 40, LAY-FOMM 60, and biocompatible polylactic acid (PLA) on the activity of murine L929 cells, gingival fibroblasts (GF), and periodontal ligament fibroblasts (PDLF) using indirect (samples on cells), direct monolayer culture models (cells on samples), and direct spheroid cultures with resazurin-based toxicity assay, confirmed by MTT and Live-dead staining. The surface topography was evaluated with scanning electron microscopy. RESULTS: The materials LAY-FOMM 40 and LAY-FOMM 60 led to a reduction in resazurin conversion in L929 cells, GF, and PDLF, higher than the impact of PLA in indirect and direct culture models. Fewer vital cells were found in the presence of LAY-FOMM 40 and 60 than PLA, in the staining in both models. In the direct model, LAY-FOMM 40 and PLA showed less impact on viability in the resazurin-based toxicity assay than in the indirect model. Spheroid microtissues showed a reduction of cell activity of GF and PDLF with LAY-FOMM 40 and 60. CONCLUSION: Overall, we found that LAY-FOMM 40 and LAY-FOMM 60 can reduce the activity of L292 and oral cells. Based on the results from the PLA samples, the direct model seems more reliable than the indirect model. CLINICAL RELEVANCE: A material modification is desired in terms of biocompatibility as it can mask the effect of drugs and interfere with the function of the 3D-printed device.

Dynamic measurement of centering forces on transvalvular cannulas.

In heart failure therapy, minimally invasive devices (transcatheter valves, catheter-based cannulas or pumps) are increasingly used. The interaction with the valve is of special importance as valve damage, backflow, and thrombus formation are known complications. Therefore, the aim of this in vitro study was to characterize the forces acting on different sized transvalvular cannulas at various transvalvular pressures for four different valves. In a pulsatile setup radial and tangential forces on transvalvular cannulas were measured for bioprosthetic, artificial pericardial tissue, fresh, and fixated porcine valves. The cannula position was varied from a central position to the wall in 10° rotational steps for the whole circular range and the use of different cannula diameters (4, 6, and 8 mm) and transvalvular pressures (40-100 mmHg). Centering forces of four different aortic valve types were identified and the three leaflets were visible in the force distribution. At the mid of the cusps and at the largest deflection the forces were highest (up to 0.8 N) and lowest in the commissures (up to 0.2 N). Whereas a minor influence of the cannula diameter was found, the transvalvular pressure linearly increased the forces but did not alter the force patterns. Centering forces that act on transvalvular cannulas were identified in an in vitro setup for several valves and valve types. Lowest centering forces were found in the commissures and highest forces were found directly at the cusps. At low pressures, low centering forces and an increased cannula movement can be expected.

The influence of left ventricular assist device inflow cannula position on thrombosis risk.

The use of left ventricular assist devices (LVADs) as a treatment method for heart failure patients has been steadily increasing; however, pathological studies showed presence of thrombi around the HeartWare ventricular assist device inflow cannula (IC) in more than 95% of patients after device explantation. Flow fields around the IC might trigger thrombus formation and require further investigation. In this study flow dynamics parameters were evaluated for different patient geometries using computational fluid dynamics (CFD) simulations. Left ventricular (LV) models of two LVAD patients were obtained from CT scans. The LV volumes of Patient 1 (P1) and Patient 2 (P2) were 264 and 114 cm3 with an IC angle of 20° and 9° from the mitral-IC tip axis at the coronal plane. The IC insertion site at the apex was central for P1, whereas it was lateral for P2. Transient CFD simulations were performed over 9 cardiac cycles. The wedge area was defined from the cannula tip to the wall of the LV apex. Mean velocity magnitude and blood stagnation region (volume with mean velocity <5 mm/s) as well as the wall shear stress (WSS) at the IC surface were calculated. Cardiac support resulted in a flow mainly crossing the ventricle from the mitral valve to the LVAD cannula for P2, while the main inflow jet deviated toward the septal wall in P1. Lower WSS at the IC surface and consequently larger stagnation volumes were observed for P2 (P1: 0.17, P2: 0.77 cm3 ). Flow fields around an LVAD cannula can be influenced by many parameters such as LV size, IC angle, and implantation site. Careful consideration of influencing parameters is essential to get reliable evaluations of the apical flow field and its connection to apical thrombus formation. Higher blood washout and lower stagnation were observed for a central implantation of the IC at the apex.

LVAD speed increase during exercise, which patients would benefit the most? A simulation study.

Patients supported with a left ventricular assist device (LVAD) have impaired cardiovascular adaptations during exercise, resulting in reduced total cardiac output and exercise intolerance. The aim of this study is to report associations among these impaired cardiovascular parameters and exercise hemodynamics, and to identify in which conditions an LVAD speed increase can provide substantial benefits to exercise. A cardiorespiratory simulator was used to reproduce the average hemodynamics of LVAD patients at exercise. Then, a sensitivity study was conducted where cardiovascular parameters were changed individually ±20% of their baseline value at exercise (heart rate, left/right ventricular contractility, total peripheral resistance, and valve pathologies). Simulations were performed at a baseline LVAD speed of 2700 rpm and repeated at 3500 rpm to evaluate the benefits of a higher LVAD support on hemodynamics. Total cardiac output (TCO) was mostly impaired by a poor left ventricular contractility or vasodilation at exercise (-0.6 L/min), followed by a poor chronotropic response (-0.3 L/min) and by a poor right ventricular contractility (-0.2 L/min). LVAD speed increase better unloads the left ventricle and improves total cardiac output in all the simulated conditions. The most substantial benefits from LVAD speed increase were observed in case of poor left ventricular contractility (TCO + 1.6 L/min) and vascular dysfunction (TCO + 1.4 L/min) followed by lower heart rate (TCO + 1.3 L/min) and impaired right ventricular contractility (TCO + 1.1 L/min). Despite the presence of the LVAD, exercise hemodynamic is strongly depending on the ability of the cardiovascular system to adapt to exercise. A poor left ventricular inotropic response and a poor vascular function can strongly impair cardiac output at exercise. In these conditions, LVAD speed increase can be an effective strategy to augment total cardiac output and unload the left ventricle. These results evidence the need to design a physiological LVAD speed controller, tailored on specific patient's needs.

Continuous LVAD monitoring reveals high suction rates in clinically stable outpatients.

Suction of the left ventricle can lead to potentially life-threatening events in left ventricular assist device (LVAD) patients. With the resolution of currently available clinical LVAD monitoring healthcare professionals are unable to evaluate patients' suction occurrences in detail. This study investigates occurrences and durations of suction events and their associations with tachycardia in stable outpatients. Continuous high-resolution LVAD data from HVAD patients were analyzed in the early outpatient period for 15 days. A validated suction detection from LVAD signals was used. Suction events were evaluated as suction rates, bursts of consecutive suction beats, and clusters of suction beats. The occurrence of tachycardia was analyzed before, during, and after suction clusters. Furthermore, blood work, implant strategy, LVAD speed setting, inflow cannula position, left ventricular diameters, and adverse events were evaluated in these patients. LVAD data of 10 patients was analyzed starting at 78 ± 22 postoperative days. Individuals' highest suction rates per hour resulted in a median of 11% (range 3%-61%). Bursts categorized as consecutive suction beats with n = 2, n = 3-5, n = 6-15, and n > 15 beats were homogenously distributed with 10.3 ± 0.8% among all suction beats. Larger suction bursts were followed by shorter suction-free periods. Tachycardia during suction occurred in 12% of all suction clusters. Significant differences in clinical parameters between individuals with high and low suction rates were only observed in left ventricular end-diastolic and end-systolic diameters (P < .02). Continuous high-resolution LVAD monitoring sheds light on outpatient suction occurrences. Interindividual and intraindividual characteristics of longitudinal suction rates were observed. Longer suction clusters have higher probabilities of tachycardia within the cluster and more severe types of suction waveforms. This work shows the necessity of improved LVAD monitoring and the implementation of an LVAD speed control to reduce suction rates and their concomitant burden on the cardiovascular system.

LVAD Pump Flow Does Not Adequately Increase With Exercise.

Left ventricular assist devices (LVADs) restore cardiovascular circulatory demand at rest with a spontaneous increase in pump flow to exercise. The relevant contribution of cardiac output provided by the LVAD and ejected through the aortic valve for exercises of different intensities has been barely investigated in patients. The hypothesis of this study was that different responses in continuous recorded pump parameters occur for maximal and submaximal intensity exercises and that the pump flow change has an impact on the oxygen uptake at peak exercise (pVO2 ). Cardiac and pump parameters such as LVAD flow rate (QLVAD ), heart rate (HR), and aortic valve (AV) opening were analyzed from continuously recorded LVAD data during physical exercises of maximal (bicycle ergometer test) and submaximal intensities (6-min walk test and regular trainings). During all exercise sessions, the LVAD speed was kept constant. Cardiac and pump parameter responses of 16 patients for maximal and submaximal intensity exercises were similar for QLVAD : +0.89 ± 0.52 versus +0.59 ± 0.38 L/min (P = 0.07) and different for HR: +20.4 ± 15.4 versus +7.7 ± 5.8 bpm (P < 0.0001) and AV-opening with 71% versus 23% of patients (P < 0.0001). Multi-regression analysis with pVO2 (R2  = 0.77) showed relation to workload normalized by bodyweight (P = 0.0002), HR response (P = 0.001), AV-opening (P = 0.02), and age (P = 0.06) whereas the change in QLVAD was irrelevant. Constant speed LVADs provide inadequate support for maximum intensity exercises. AV-opening and improvements in HR show an important role for higher exercise capacities and reflect exercise intensities. Changes in pump flow do not impact pVO2 and are independent of AV-opening and response in HR. An LVAD speed control may lead to adequate left ventricular support during strenuous physical activities.

Beat-to-beat detection of aortic valve opening in HeartWare left ventricular assist device patients.

Continuous flow left ventricular assist devices (cfLVADS) result in a significant reduction in aortic valve (AV) opening, which has been associated with several complications. Reliable monitoring of AV opening is needed to determine whether pump speed adjustment may be able to minimize adverse outcomes. We assessed AV status continuously by echocardiography for 4 minutes in 3 states in 18 HeartWare HVAD patients: 2 minutes at rest, and 1 minute each following Valsalva maneuver and supine leg-raising. Using a previously described algorithm, beat-to-beat AV status was compared with the area under the curve of the normalized power spectral density analysis (PSD-AUC) for the corresponding beats of the pump speed waveform. Five thousand five hundred twenty-seven beats were analyzed. AV opening varied between 0% and 100% for the cohort with the median AV opening frequency 21.5%, and median duration of opening of 124 msec (range 0-279). The receiver operating characteristic (ROC) curve area for AV opening by the PSD-AUC algorithm was 0.95 (P < 0.0001). A PSD-AUC cut-off of 0.82 distinguished between an open and closed AV with 86% sensitivity and 93% specificity. Accuracy was similar in regular cardiac rhythm, atrial fibrillation or with frequent ventricular ectopic beats. Valsalva maneuver and leg-raising had no impact on accuracy. The PSD-AUC was strongly predictive of AV opening duration (P < 0.0001). We found that AV status and opening duration can be determined with high accuracy on a beat-to-beat basis irrespective of cardiac rhythm and with low level exercise and changes in filling.

A Standardized Telephone Intervention Algorithm Improves the Survival of Ventricular Assist Device Outpatients.

Ventricular assist devices (VADs) are an established therapeutic option for patients with chronic heart failure. Continuous monitoring of VAD parameters and their adherence to guidelines are crucial to detect problems in an early stage to optimize outcomes. A telephone intervention algorithm for VAD outpatients was developed, clinically implemented and evaluated. During the phone calls, a structured inquiry of pump parameters, alarms, blood pressure, INR, body weight and temperature, exit-site status and heart failure symptoms was performed and electronically categorized by an algorithm into 5 levels of severity. VAD outpatient outcomes without (n = 71) and with bi-weekly telephone interviews in their usual care (n = 25) were conducted using proportional hazard Cox regression, with risk adjustment based on a propensity score model computed from demographics and risk factors. From February 2015 through October 2017, 25 patients (n = 3 HeartMate II, n = 4 HeartMate 3 and n = 18 HeartWare HVAD) underwent 637 telephone interventions. In 57.5% of the calls no problems were identified, 3.9% were recalled on the next day because of alarms. In 26.5% (n = 169), the VAD Coordinator had to refer to the physician due to elevated blood pressure (n = 125, >85 mm Hg), INR < 2.0 or > 4.0 (n = 24) or edema (n = 10), 11.9% of the calls led to a follow-up because of equipment or exit-site problems. Propensity-adjusted 2-year survival (89% vs. 57%, P = 0.027) was significantly higher for the telephone intervention group. Continuous, standardized communication with VAD outpatients is important for early detection of upcoming problems and leads to significantly improved survival.

Interaction of a Transapical Miniaturized Ventricular Assist Device With the Left Ventricle: Hemodynamic Evaluation and Visualization in an Isolated Heart Setup.

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.

Pump Speed Waveform Analysis to Detect Aortic Valve Opening in Patients on Ventricular Assist Device Support.

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.

Assessment of aortic valve opening during rotary blood pump support using pump signals.

During left ventricular support by rotary blood pumps (RBPs), the biomechanics of the aortic valve (AV) are altered, potentially leading to adverse events like commissural fusion, valve insufficiency, or thrombus formation. To avoid these events, assessment of AV opening and consequent adaptation of pump speed seem important. Additionally, this information provides insight into the heart-pump interaction. The aim of this study was to develop a method to assess AV opening from the pump flow signal. Data from a numerical model of the cardiovascular system and animal experiments with an RBP were employed to detect the AV opening from the flow waveform under different hemodynamic conditions. Three features calculated from the pump flow waveform were used to classify the state of the AV: skewness, kurtosis, and crest factor. Three different classification algorithms were applied to determine the state of the AV based on these features. In the model data, the best classifier resulted in a percentage of correctly identified beats with a closed AV (specificity) of 99.9%. The percentage of correctly identified beats with an open AV (sensitivity) was 99.5%. In the animal experiments, specificity was 86.8% and sensitivity reached 96.5%. In conclusion, a method to detect AV opening independently from preload, afterload, heart rate, contractility, and degree of support was developed. This algorithm makes the evaluation of the state of the AV possible from pump data only, allowing pump speed adjustment for a frequent opening of the AV and providing information about the interaction of the native heart with the RBP.

Continuous monitoring of cardiac rhythms in left ventricular assist device patients.

Monitoring of cardiac rhythms is of major importance in the treatment of heart failure patients with left ventricular assist devices (LVADs) implanted. A continuous surveillance of these rhythms could improve out-of-hospital care in these patients. The aim of this study was to investigate cardiac rhythms using available pump data only. Datasets (n = 141) obtained in the normal ward, in the intensive care unit, and during bicycle ergometry were analyzed in 11 recipients of a continuous flow LVAD (59.1 ± 9.7 years; male 82%). Tachograms and arrhythmic patterns derived from the pump flow waveform, and a simultaneously recorded ECG were compared, as well as heart rate variability parameters such as: the average heart beat duration (RR interval), the standard deviation of the beat duration (SDNN), the root-mean-square of the difference of successive beat durations (RMSSD), and the number of pairs of adjacent beat duration differing by >50 ms divided by the number of all beats (pNN50). A very good agreement of cardiac rhythm parameters from the pump flow compared with ECG was found. Tachycardia, atrial fibrillation, and extrasystoles could be accurately identified from the tachograms derived from the pump flow. Also, Bland-Altman analysis comparing pump flow with ECG indicated a very small difference in average RR interval of 0.3 ± 1.0 ms, in SSDN of 0.5 ± 2.7 ms, in RMSSD of 1.0 ± 5.6 ms, and in pNN50 of 0.3 ± 1.0%. Continuous monitoring of cardiac rhythms from available pump data is possible. It has the potential to reduce the out-of-hospital diagnostic burden and to permit a more efficient adjustment of the level of mechanical support.

Measured and simulated mechanical properties of additively manufactured matrix-inclusion multimaterials fabricated by material jetting.

Modern additive manufacturing enables the simultaneous processing of different materials during the printing process. While multimaterial 3D printing allows greater freedom in part design, the prediction of the mix-material properties becomes challenging. One type of multimaterials are matrix-inclusion composites, where one material contains inclusions of another material. Aim of this study was to develop a method to predict the uniaxial Young's modulus and Poisson's ratio of material jetted matrix-inclusion composites by a combination of simulations and experimental data.Fifty samples from commercially available materials in their pure and matrix-inclusion mixed forms, with cubic inclusions, have been fabricated using material jetting and mechanically characterized by uniaxial tensile tests. Multiple simulation approaches have been assessed and compared to the measurement results in order to find and validate a method to predict the multimaterials' properties. Optical coherence tomography and microscopy was used to characterize the size and structure of the multimaterials, compared to the design.The materials exhibited Young's moduli in the range of 1.4 GPa to 2.5 GPa. The multimaterial mixtures were never as stiff as the weighted volume average of the primary materials (up to [Formula: see text] softer for 45% RGD8530-DM inclusions in VeroClear matrix). Experimental data could be predicted by finite element simulations by considering a non-ideal contact stiffness between matrix and inclusion ([Formula: see text] for RGD8530-DM, [Formula: see text] for RGD8430-DM), and geometries of the printed inclusions that deviated from the design (rounded edge radii of [Formula: see text]m). Not considering this would lead to a difference of the estimation result of up to [Formula: see text]MPa (44%), simulating an inclusion volume fraction of 45% RGD8530-DM.Prediction of matrix-inclusion composites fabricated by multimaterial jetting printing, is possible, however, requires a priori knowledge or additional measurements to characterize non-ideal contact stiffness between the components and effective printed geometries, precluding therefore a simple multimaterial modelling.

Importance of cardiac-synchronized vagus nerve stimulation parameters on the provoked chronotropic response for different levels of cardiac innervation.

Introduction: The influence of vagus nerve stimulation (VNS) parameters on provoked cardiac effects in different levels of cardiac innervation is not well understood yet. This study examines the effects of VNS on heart rate (HR) modulation across a spectrum of cardiac innervation states, providing data for the potential optimization of VNS in cardiac therapies. Materials and Methods: Utilizing previously published data from VNS experiments on six sheep with intact innervation, and data of additional experiments in five rabbits post bilateral rostral vagotomy, and four isolated rabbit hearts with additionally removed sympathetic influences, the study explored the impact of diverse VNS parameters on HR. Results: Significant differences in physiological threshold charges were identified across groups: 0.09 ± 0.06 µC for intact, 0.20 ± 0.04 µC for vagotomized, and 9.00 ± 0.75 µC for isolated hearts. Charge was a key determinant of HR reduction across all innervation states, with diminishing correlations from intact (r = 0.7) to isolated hearts (r = 0.44). An inverse relationship was observed for the number of pulses, with its influence growing in conditions of reduced innervation (intact r = 0.11, isolated r = 0.37). Frequency and stimulation delay showed minimal correlations (r < 0.17) in all conditions. Conclusion: Our study highlights for the first time that VNS parameters, including stimulation intensity, pulse width, and pulse number, crucially modulate heart rate across different cardiac innervation states. Intensity and pulse width significantly influence heart rate in innervated states, while pulse number is key in denervated states. Frequency and delay have less impact impact across all innervation states. These findings suggest the importance of customizing VNS therapy based on innervation status, offering insights for optimizing cardiac neuromodulation.