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.

A novel ex-vivo isolated rabbit heart preparation to explore the cardiac effects of cervical and cardiac vagus nerve stimulation.

The cardiac responses to vagus nerve stimulation (VNS) are still not fully understood, partly due to uncontrollable confounders in the in-vivo experimental condition. Therefore, an ex-vivo Langendorff-perfused rabbit heart with intact vagal innervation is proposed to study VNS in absence of cofounding anesthetic or autonomic influences. The feasibility to evoke chronotropic responses through electrical stimulation ex-vivo was studied in innervated isolated rabbit hearts (n = 6). The general nerve excitability was assessed through the ability to evoke a heart rate (HR) reduction of at least 5 bpm (physiological threshold). The excitability was quantified as the charge needed for a 10-bpm HR reduction. The results were compared to a series of in-vivo experiments rabbits (n = 5). In the ex-vivo isolated heart, the baseline HR was about 20 bpm lower than in-vivo (158 ± 11 bpm vs 181 ± 19 bpm). Overall, the nerve remained excitable for about 5 h ex-vivo. The charges required to reduce HR by 5 bpm were 9 ± 6 µC and 549 ± 370 µC, ex-vivo and in-vivo, respectively. The charges needed for a 10-bpm HR reduction, normalized to the physiological threshold were 1.78 ± 0.8 and 1.22 ± 0.1, in-vivo and ex-vivo, respectively. Overall, the viability of this ex-vivo model to study the acute cardiac effects of VNS was demonstrated.

Quantification of paravalvular leaks associated with TAVI implants using 4D MRI in an aortic root phantom made possible by the use of 3D printing.

Introduction: Transcatheter aortic valve implantation (TAVI) has become an alternative to surgical replacement of the aortic valve elderly patients. However, TAVI patients may suffer from paravalvular leaks (PVL). Detecting and grading is usually done by echocardiography, but is limited by resolution, 2D visualization and operator dependency. 4D flow magnetic resonance imaging (MRI) is a promising alternative, which did not reach clinical application in TAVI patients. The aim of this study was applying 3D printing technologies in order to evaluate flow patterns and hemodynamics of PVLs following TAVI, exploiting 4D flow MRI and standard ultrasound. Materials and methods: An MR-compatible, anatomically left ventricle, aortic root, and ascending aorta model was fabricated by combining 3D-printed parts and various soft silicone materials to match physiological characteristics. An Abbott Portico™ valve was used in continuous antegrade flow (12-22 l/min), retrograde flow with varying transvalvular pressures (60-110 mmHg), and physiological pulsatile hemodynamics (aortic pressure: 120/80 mmHg, cardiac output: 5 l/min) Time-resolved MR measurements were performed above and below the TAVI stent and compared with color Doppler ultrasound measurements in exactly the same setup. Results: The continuous antegrade flow measurements from MRI largely agreed with the flowmeter measurements, and a maximum error of only 7% was observed. In the retrograde configuration, visualization of the paravalvular leaks was possible from the MR measurements, but flow was overestimated by up to 33%. The 4D MRI measurement in the pulsatile setup revealed a single main PVL, which was also confirmed by the color Doppler measurements, and velocities were similar (2.0 m/s vs. 1.7 m/s). Discussion: 4D MRI techniques were used to qualitatively assess flow in a patient-specific, MR-compatible and flexible model, which only became possible through the use of 3D printing techniques. Flow patterns in the ascending aorta, identification and quantification of PVLs was possible and the location and extent of PVLs were confirmed by ultrasound measurements. The 4D MRI flow technique allowed evaluation of flow patterns in the ascending aorta and the left ventricle below the TAVI stent with good results in identifying PVLs, demonstrating its capabilities over ultrasound by providing the ability to visualize the paravalvular jets in three dimensions at however, additional expenditure of time and money.

Left atrial appendage occlusion in ventricular assist device patients to decrease thromboembolic events: A computer simulation study.

Atrial fibrillation (AF) is a common comorbidity in left ventricular assist device (LVAD) patients and has been identified as a risk factor for thromboembolic stroke. Blood stagnation within the left atrial appendage (LAA) is considered a possible major source of thrombosis and clinical studies have shown reduced thromboembolic risk after LAA occlusion (LAAO). Therefore, this study aims to investigate the effect of LAAO on thrombosis-related parameters using patient-specific simulations. Left ventricular and left atrial geometries of an LVAD patient were obtained from computed tomography and combined with hemodynamic data with either sinus rhythm (SR) or AF generated by a lumped parameter model. In four simulations applying contractile walls, stagnation volume and blood residence times were evaluated with or without AF and with or without LAAO. Reduced atrial contraction in AF resulted in unfavorable flow dynamics within the left atrium. The average atrial velocity was lower for the AF simulation when compared to SR, resulting in a 55% increase in the atrial stagnation volume (from 4.2 to 6.5 cm3). Moreover, blood remained in the LAA for more than 8 cardiac cycles. After LAAO the atrial stagnation decreased from 4.2 to 1.4 cm3 for SR and from 6.5 to 2.3 cm3 for the AF simulation. A significant stagnation volume was found in the LAA for both SR and AF, with larger values occurring with AF. These regions are known as potential sources for thrombus formation and can be diminished by LAAO. This significantly improved the thrombus-related flow parameters and may also lower the risk of thromboembolic events from the appendage.

A Sensorless Modular Multiobjective Control Algorithm for Left Ventricular Assist Devices: A Clinical Pilot Study.

Background: Contemporary Left Ventricular Assist Devices (LVADs) mainly operate at a constant speed, only insufficiently adapting to changes in patient demand. Automatic physiological speed control promises tighter integration of the LVAD into patient physiology, increasing the level of support during activity and decreasing support when it is excessive. Methods: A sensorless modular control algorithm was developed for a centrifugal LVAD (HVAD, Medtronic plc, MN, USA). It consists of a heart rate-, a pulsatility-, a suction reaction-and a supervisor module. These modules were embedded into a safe testing environment and investigated in a single-center, blinded, crossover, clinical pilot trial (clinicaltrials.gov, NCT04786236). Patients completed a protocol consisting of orthostatic changes, Valsalva maneuver and submaximal bicycle ergometry in constant speed and physiological control mode in randomized sequence. Endpoints for the study were reduction of suction burden, adequate pump speed and flowrate adaptations of the control algorithm for each protocol item and no necessity for intervention via the hardware safety systems. Results: A total of six patients (median age 53.5, 100% male) completed 13 tests in the intermediate care unit or in an outpatient setting, without necessity for intervention during control mode operation. Physiological control reduced speed and flowrate during patient rest, in sitting by a median of -75 [Interquartile Range (IQR): -137, 65] rpm and in supine position by -130 [-150, 30] rpm, thereby reducing suction burden in scenarios prone to overpumping in most tests [0 [-10, 2] Suction events/minute] in orthostatic upwards transitions and by -2 [-6, 0] Suction events/min in Valsalva maneuver. During submaximal ergometry speed was increased by 86 [31, 193] rpm compared to constant speed for a median flow increase of 0.2 [0.1, 0.8] L/min. In 3 tests speed could not be increased above constant set speed due to recurring suction and in 3 tests speed could be increased by up to 500 rpm with a pump flowrate increase of up to 0.9 L/min. Conclusion: In this pilot study, safety, short-term efficacy, and physiological responsiveness of a sensorless automated speed control system for a centrifugal LVAD was established. Long term studies are needed to show improved clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04786236.

When Nothing Goes Right: Risk Factors and Biomarkers of Right Heart Failure after Left Ventricular Assist Device Implantation.

Right heart failure (RHF) is a severe complication after left ventricular assist device (LVAD) implantation. The aim of this study was to analyze the incidence, risk factors, and biomarkers for late RHF including the possible superiority of the device and implantation method. This retrospective, single-center study included patients who underwent LVAD implantation between 2014 and 2018. Primary outcome was freedom from RHF over one-year after LVAD implantation; secondary outcomes included pre- and postoperative risk factors and biomarkers for RHF. Of the 145 consecutive patients (HeartMate 3/HVAD: n = 70/75; female: 13.8%), thirty-one patients (21.4%) suffered RHF after a mean LVAD support of median (IQR) 105 (118) days. LVAD implantation method (less invasive: 46.7% vs. 35.1%, p = 0.29) did not differ significantly in patients with or without RHF, whereas the incidence of RHF was lower in HeartMate 3 vs. HVAD patients (12.9% vs. 29.3%, p = 0.016). Multivariate Cox proportional hazard analysis identified HVAD (HR 4.61, 95% CI 1.12-18.98; p = 0.03), early post-op heart rate (HR 0.96, 95% CI 0.93-0.99; p = 0.02), and central venous pressure (CVP) (HR 1.21, 95% CI 1.05-1.39; p = 0.01) as independent risk factors for RHF, but no association of RHF with increased all-cause mortality (HR 1.00, 95% CI 0.99-1.01; p = 0.50) was found. To conclude, HVAD use, lower heart rate, and higher CVP early post-op were independent risk factors for RHF following LVAD implantation.

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.

Effects of the atrium on intraventricular flow patterns during mechanical circulatory support.

Simulations of the ventricular flow patterns during left ventricular assist device (LVAD) support are mainly performed with idealized cylindrical inflow, neglecting the influence of the atrial vortex. In this study, the influence of the left atrium (LA) on the intra-ventricular flow was investigated via Computational Fluid Dynamics (CFD) simulations. Ventricular flow was simulated by a combined Eulerian (carrier flow)/Lagrangian (particles) approach taking into account either the LA or a cylindrical inflow section to mimic a fully support condition. The flow deviation at the mitral valve, the blood low-velocity volume as well as the residence time and shear stress history of the particles were calculated. Inclusion of the LA deflects the flow at the mitral valve by 25°, resulting in an asymmetric flow jet entering the left ventricle. This reduced the ventricular low-velocity volume by 40% (from 6.4 to 3.9 cm3), increased (40%) the shear stress experienced by particles and correspondingly increased (27%) their residence time. Under the studied conditions, the atrial geometry plays a major role in the development of intraventricular flow patterns. A reliable prediction of blood flow dynamics and consequently thrombosis risk analysis within the ventricle requires the consideration of the LA in computational simulations.

Pump position and thrombosis in ventricular assist devices: Correlation of radiographs and CT data.

Malpositioning of left ventricular assist devices (LVAD) is a risk factor for thrombosis, but its identification from clinical imaging remains challenging. X-rays and CT scans were analyzed and parameters identified that correlated to pump thrombosis. Retrospective imaging data of patients (n = 115) with HeartmateII (HMII) or HVAD were analyzed in two groups (pump-thrombosis PT, n = 15 vs matched control group NT, n = 15) using routine X-rays and CT scans. In CT, directional deviations of the inflow cannula in three-chamber and two-chamber view (α and ß angles) were identified. In HVAD PT frontal radiographs showed reduced pump body area and smaller minor axis (PT 41.3 ± 4.8 mm vs NT 34.9 ± 6.0 mm, p = 0.026), and in the lateral radiographs the visibility of the inflow cannula served as a predictive parameter for PT. In HMII patients, no parameters were associated with PT. The angle α differed significantly (NT -1.2 ± 7.5°, PT -22.0 ± 4.7°, p = 0.006) in HVAD patients. Further, correlations of x-ray parameters with CT angles α and ß showed that radiographs can be used to identify malpositioned pumps. Well-aligned inflow cannula positions are essential. HVAD patients with a posterior rotation of the inflow cannula have a higher risk of pump thrombosis. This risk can reliably be identified from routine radiographs.

Effect of Timings of the Lavare Cycle on the Ventricular Washout in an In Vitro Flow Visualization Setup.

Left ventricular assist devices inherently alter the intraventricular flow field and create areas of blood stasis with potential thrombus formation. The Lavare cycle of the Medtronic HeartWare HVAD was designed to improve ventricular washout. This study aims to evaluate its effects on ventricular washout in a pulsatile in vitro setting with a focus on the timing of pump speed changes. Ventricular flow fields were obtained via particle image velocimetry in two modes: With constant left ventricular assist devices speed and with the Lavare cycle applied. The start of the Lavare cycle was shifted over an entire cardiac cycle, and ventricular washout was evaluated based on velocity fields, kinetic energy, and normalized pulsatility of flow fields. The ventricular flow fields showed dependence on the timing of the Lavare cycle and interaction between speed changes and the cardiac phase. Higher apical velocity was observed for speed decreases at the late E wave and for increases at mid systole by 29% (P = 0.002) and 61% (P < 0.001), respectively. Mean apical kinetic energy for these phases also increased by 21% (P = 0.0013) and 46% (P < 0.001). The Lavare cycle generally promotes higher apical washout and can specifically generate further improved washout if speed steps are applied at the correct timing on the cardiac cycle.

Validation of numerically simulated ventricular flow patterns during left ventricular assist device support.

Intraventricular flow patterns during left ventricular assist device support have been investigated via computational fluid dynamics by several groups. Based on such simulations, specific parameters for thrombus formation risk analysis have been developed. However, computational fluid dynamic simulations of complex flow configurations require proper validation by experiments. To meet this need, a ventricular model with a well-defined inflow section was analyzed by particle image velocimetry and replicated by transient computational fluid dynamic simulations. To cover the laminar, transitional, and turbulent flow regime, four numerical methods including the laminar, standard k-omega, shear-stress transport, and renormalized group k-epsilon were applied and compared to the particle image velocimetry results in 46 different planes in the whole left ventricle. The simulated flow patterns for all methods, except renormalized group k-epsilon, were comparable to the flow patterns measured using particle image velocimetry (absolute error over whole left ventricle: laminar: 10.5, standard k-omega: 11.3, shear-stress transport: 11.3, and renormalized group k-epsilon: 17.8 mm/s). Intraventricular flow fields were simulated using four numerical methods and validated with experimental particle image velocimetry results. In the given setting and for the chosen boundary conditions, the laminar, standard K-omega, and shear-stress transport methods showed acceptable similarity to experimental particle image velocimetry data, with the laminar model showing the best transient behavior.

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.

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.

Comparative analysis of cardiac mechano-energetics in isolated hearts supported by pulsatile or rotary blood pumps.

The previously more frequently implanted pulsatile blood pumps (PBPs) showed higher recovery rates than the currently preferred rotary blood pumps (RBPs), with unclear causality. The aim of this study was to comparatively assess the capability of PBPs and RPBs to unload the left ventricle and maintain cardiac energetics as a possible implication for recovery. An RBP and a heartbeat synchronized PBP were alternately connected to isolated porcine hearts. Rotational speed of RBPs was set to different support levels. For PBP support, the start of ejection was phased to different points during the cardiac cycle, prescribed as percentage delays from 0% to 90%. Cardiac efficiency, quantified by the ratio of external work over myocardial oxygen consumption, was determined. For RBP support, higher degrees of RBP support correlated with lower left atrial pressures (LAP) and lower cardiac efficiency (r = 0.91 ± 0.12). In contrast, depending on the phase delay of a PBP, LAP and cardiac efficiency exhibited a sinusoidal relationship with the LAP minimum at 90% and efficiency maximum at 60%. Phasing of a PBP offers the possibility to maintain a high cardiac efficiency and simultaneously unload the ventricle. These results warrant future studies investigating whether optimized cardiac energetics promotes functional recovery with LVAD therapy.

Evaluation of the HeartWare ventricular assist device Lavare cycle in a particle image velocimetry model and in clinical practice.

OBJECTIVES: Ventricular blood stasis is a concern for continuous flow mechanical support devices and might contribute to the formation of thromboembolic events. The HeartWare® Ventricular Assist System (HVAD®) is equipped with the Lavare™ cycle that is a periodic speed modulation feature designed to alter flow patterns within the left ventricle and reduce areas of potential blood stasis. Here, we report in vitro and clinical findings on the effects of the Lavare cycle. METHODS: The effect of pump speed changes on the intraventricular flow field was examined with an in vitro particle image velocimetry model. The clinical impact of the Lavare cycle was evaluated through a retrospective review of the ReVOLVE study which includes 248 patients implanted with the HVAD following Conformité Européenne Mark in nine centres in Europe and Australia. Baseline characteristics, adverse event profiles and Kaplan-Meier survival estimates were stratified by patients using/not using the Lavare cycle. RESULTS: Particle image velocimetry showed increased ventricular washout with an active Lavare cycle as measured by the fluid velocities and angular dispersion parameters. With the Lavare cycle on, there was also a 22% decrease in the stagnation index compared with when the Lavare cycle was off. In the ReVOLVE registry, patients with the Lavare cycle turned on (n = 215) were supported for 497 patient-years, whereas patients who did not use the speed modulation (n = 33) were supported for 39.3 patient-years. The Lavare cycle did not significantly affect patient survival as both groups had approximately an 80% survival after 1 year. Patients using the Lavare cycle had significantly fewer rates of stroke [0.06 vs 0.20 events per patient-year (EPPY), P = 0.0008], sepsis (0.03 vs 0.15 EPPY, P = 0.0003) and right heart failure (0.03 vs 0.18 EPPY, P < 0.0001) with no difference in the transplant or recovery rates among the two cohorts. CONCLUSIONS: The Lavare cycle effectively generates ventricular washout and the adverse event profiles of ReVOLVE patients with the Lavare cycle on were better than those with the Lavare cycle off. Larger studies are warranted to verify the positive effect of the Lavare cycle and to optimize speed modulation settings, so additional clinically relevant improvements can be realized.

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.

The influence of bicuspid aortic valves on the dynamic pressure distribution in the ascending aorta: a porcine ex vivo model.

OBJECTIVES: The aim of the study was to simulate the effect of different bicuspid aortic valve configurations on the dynamic pressure distribution in the ascending aorta. METHODS: Aortic specimens were harvested from adult domestic pigs. In Group 1, bicuspidalization was created by a running suture between the left and the right coronary leaflets (n = 6) and in Group 2 by a running suture between the left and the non-coronary leaflets (n = 6). Eleven tricuspid specimens served as controls. Two intraluminal pressure catheters were positioned at the concavity and the convexity of the ascending aorta. The specimens were connected to a mock circulation (heart rate: 60 bpm, target pressure: 95 mmHg). A comparison of the different conditions was also done in a numerical simulation. RESULTS: At a distal mean aortic pressure of 94 ± 10 mmHg, a mean flow rate of 5.2 ± 0.3 l/min was achieved. The difference of maximal dynamic pressure values (which occurred in systole) between locations at the convexity and the concavity was 7.8 ± 2.9 mmHg for the bicuspid and 1.0 ± 0.9 mmHg for the tricuspid specimens (P < 0.001). The numerical simulation revealed an even higher pressure difference between convexity and concavity for bicuspid formation. CONCLUSIONS: In this hydrodynamic mock circulation model, we were able to demonstrate that bicuspid aortic valves are associated with significant pressure differences in different locations within the ascending aorta compared with tricuspid aortic valves. These altered pressure distributions and flow patterns may further add to the understanding of aneurismal development in patients with bicuspid aortic valves and might serve to anticipate adverse aortic events due to a better knowledge of the underlying mechanisms.

Investigation of hemodynamics in the assisted isolated porcine heart.

BACKGROUND: Currently, the interaction between rotary blood pumps (RBP) and the heart is investigated in silico, in vitro, and in animal models. Isolated and defined changes in hemodynamic parameters are unattainable in animal models, while the heart-pump interaction in its whole complexity cannot be modeled in vitro or in silico. AIM: The aim of this work was to develop an isolated heart setup to provide a realistic heart-pump interface with the possibility of easily adjusting hemodynamic parameters. METHODS: A mock circuit mimicking the systemic circulation was developed. Eight porcine hearts were harvested using a protocol similar to heart transplantation. Then, the hearts were resuscitated using Langendorff perfusion with rewarmed, oxygenated blood. An RBP was implanted and the setup was switched to the "working mode" with the left heart and the RBP working as under physiologic conditions. Both the unassisted and assisted hemodynamics were monitored. RESULTS: In the unassisted condition, cardiac output was up to 9.5 l/min and dP/dtmax ranged from 521 to 3621 mmHg/s at a preload of 15 mmHg and afterload of 70 mmHg. With the RBP turned on, hemodynamics similar to heart-failure patients were observed in each heart. Mean pump flow and flow pulsatility ranged from 0 to 11 l/min. We were able to reproduce conditions with an open and closed aortic valve as well as suction events. CONCLUSIONS: An isolated heart setup including an RBP was developed, which combines the advantages of in silico/vitro methods and animal experiments. This tool thus provides further insight into the interaction between the heart and an RBP.

Sternal force distribution during median sternotomy retraction.

BACKGROUND: Median sternotomy is the access of choice in cardiac surgery. Sternal retractors exert significant forces on the thoracic cage and might cause considerable damage. The aim of this study was to determine the effects of retractor shape on local force distribution to obtain criteria for retractor design. METHODS: Two types of sternal retractors (straight [SSR] and curved [CSR]) were equipped with force sensors. Force distribution, total force, and displacement were recorded to a spread width of 10 cm in 18 corpses (11 males and 7 females; age, 62 ± 12 years). Both retractors were used in alternating sequence in 4 iterations in every corpse. Data were compared with respect to the different retractor blade shapes. RESULTS: Maximum total forces for full retraction of both retractors resulted in 349.4 ± 77.9 N. Force distribution during the first retraction for the cranial/median/caudal part of the sternum was 101.5 ± 43.9/29.1 ± 33.9/63.0 ± 31.4 N for the SSR and 38.7 ± 41.3/80.9 ± 64.5/34.0 ± 25.8 N for the CSR, respectively. During the 4 spreading cycles, the average force decreased from 224.6 ± 61.3 N in the first to 110.8 ± 39.8 N in the fourth iteration. The mean total force for the first retraction revealed 226.4 ± 71.9 N for the CSR and 222.8 ± 52.9 N for the SSR. CONCLUSIONS: The shape of sternal retractors considerably influences the force distribution on the sternal incision. In the SSR, forces on the cranial and caudal sternum are significantly higher than in the median section, whereas in the CSR, forces in the median section are highest.

Fixation and mounting of porcine aortic valves for use in mock circuits.

PURPOSE: Investigations of the circulatory system in vitro use mock circuits that require valves to mimic the cardiac situation. Whereas mechanical valves increase water hammer effects due to inherent stiffness and do not allow the use of pressure lines or catheters, bioprosthetic valves are expensive and of limited durability in test fluids. Therefore, we developed a cheap, fast, alternative method to mount valves obtained from the slaughterhouse in mock circuits. METHODS: Porcine aortic roots were obtained from the abattoir and used either in native condition or after fixation. Fixation was performed at a constant retrograde pressure to ensure closed valve position. Fixation time was 4 h in a 0.5%-glutaraldehyde phosphate buffer. The fixed valves were molded into a modular mock circulation connector using a fast curing silicone. Valve functionality was evaluated in a pulsatile setting (cardiac output = 4.7 l/min, heart rate = 80 beats/min) and compared before and after fixation. Leaflet motion was recorded with a high-speed camera and valve insufficiency was quantified by leakage flow under steady pressure application (80 mmHg). RESULTS: Under physiological conditions the aortic valves showed almost equal leaflet motion in native and fixed conditions. However, the leaflets of the native valves showed lower stiffness and more fluttering during systole than the fixed specimens. Under retrograde pressure, fresh and fixed valves showed small leakage flows of <30 ml/min. CONCLUSIONS: The new mounting and fixation procedure is a fast method to fabricate low cost biologic valves for the use in mock circuits.