Native Left Ventricle Research Articles

Identification of left ventricular flow features in healthy and pathological conditions

Abstract Background In the presence of mitral valve diseases or following surgical interventions, the hemodynamics in the left ventricle (LV) are significantly altered [1]. These maladaptive intraventricular hemodynamic alterations can stimulate a cascade of events leading to progressive adverse LV remodeling and eventual heart failure [2]. Qualitative and quantitative evaluation of LV flow features may provide a potential for sensitive risk stratification of clinical cardiac function [3]. Purpose The purpose of this study is to identifying LV flow features using in vitro experiments under both normal and pathological conditions, including mitral regurgitation (MR), mitral valve replacement with bioprosthetic/mechanical valve, and transcatheter mitral valve edge-to-edge repair (TEER). Methods We utilized a biohybrid approach to construct the in vitro experimental platform, where the native mitral valve (including chordae tendineae and papillary muscles) and aortic valve from porcine were combined with a 3D-printed silicon LV (figure 1). To ensure comparability across different conditions, we maintained consistency by utilizing the same native valve and 3D-printed LV. For pathological conditions, we cut the chordae tendineae in A2 zone to induce the severe degenerative MR, and TEER was performed on this prolapsed valve by placing two clips in A2-P2 zone. Then, the anterior leaflet of valve was cut, and a bioprosthetic valve and mechanical valve were sutured to mitral annulus to simulate surgical valve replacement, respectively. Left ventricular flow fields were measured using four-dimensional particle image velocimetry (4D-PIV) technique, with vector interval of 0.9 mm in all the spatial directions and temporal resolution of 10 ms. Results Significant differences in mean flow field were observed among healthy and pathological conditions (figure 2). Firstly, the vortex orientation was clockwise in healthy, MR, bioprosthetic valve replacement, and TEER conditions, which could accompany the redirection of blood flows towards the aortic valve. However, the replacement with a mechanical valve resulted in an alteration in vortex orientation from clockwise to counterclockwise. Secondly, the position of the center of the vortex changed in pathological conditions, with the center of the vortex closest to the apex and the left ventricle outflow tract in the healthy condition. Thirdly, the maximum Reynolds shear stress (RSS), which may be responsible for thrombus formation, significantly increased after TEER procedure and bioprosthetic valve replacement. Conclusions This study demonstrates significant changes in LV hemodynamics across different conditions. The flow features, including vortex orientations, vortex positions and the RSS, may potentially become crucial considerations for the optimization of artificial valves and mitral valve repair devices.Figure 1 Figure 2

Design and Analysis of a Polymeric Left Ventricular Simulator via Computational Modelling.

Preclinical testing of medical devices is an essential step in the product life cycle, whereas testing of cardiovascular implants requires specialised testbeds or numerical simulations using computer software Ansys 2016. Existing test setups used to evaluate physiological scenarios and test cardiac implants such as mock circulatory systems or isolated beating heart platforms are driven by sophisticated hardware which comes at a high cost or raises ethical concerns. On the other hand, computational methods used to simulate blood flow in the cardiovascular system may be simplified or computationally expensive. Therefore, there is a need for low-cost, relatively simple and efficient test beds that can provide realistic conditions to simulate physiological scenarios and evaluate cardiovascular devices. In this study, the concept design of a novel left ventricular simulator made of latex rubber and actuated by pneumatic artificial muscles is presented. The designed left ventricular simulator is geometrically similar to a native left ventricle, whereas the basal diameter and long axis length are within an anatomical range. Finite element simulations evaluating left ventricular twisting and shortening predicted that the designed left ventricular simulator rotates approximately 17 degrees at the apex and the long axis shortens around 11 mm. Experimental results showed that the twist angle is 18 degrees and the left ventricular simulator shortens 5 mm. Twist angles and long axis shortening as in a native left ventricle show it is capable of functioning like a native left ventricle and simulating a variety of scenarios, and therefore has the potential to be used as a test platform.

BIO30: A Method to Monitor Ventricular Recovery Using VAD Signals Based on Parseval’s Power Theorem

Study: Recent studies highlight the growing interest in achieving ventricular recovery for VAD patients, thereby eliminating the need for cardiac transplantation. Hemodynamic measurements may be performed during periodic echocardiography for patients with probable recovery. However, there are no standard methods to evaluate ventricular recovery on a continuous outpatient basis. Such a method can help assess changes in cardiac function throughout daily activities, potentially optimized by a responsive VAD control algorithm. The objective of this study was to evaluate a surrogate measure of cardiac contractility based on VAD inherent signals using an in-silico simulation model of assisted circulation. Methods: Without loss of generality, hemodynamic power can be visualized as an electrical power signal in an implanted VAD. The power of a continuous periodic signal (the VAD Flow Rate signal), given by Parseval’s Power Theorem, is equivalently the average value integral over one period of the square of the magnitude of the signal (inclusive of all harmonic components). In this in-silico simulation study, we compute the ratio of this power with the norm (over multiple cardiac cycles) of the signal under steady-state conditions. We call this ratio the Power Factor of the VAD Flow Rate, represented by λVAD. Numerical simulations were conducted for different values of ventricular contractility (Emax Maximum Ventricular Elastance) from 0.5 to 2.0 mmHg/ml over a range of VAD speeds of 1000 to 8000 RPM (HeartMate 3® VAD Model) in steps of 100 RPM. Results: The figure below illustrates the relationship of the Power Factor to VAD speed for four levels of ventricular contractility. At 1000 RPM, the Power Factor for all Emax values was found to be equal. As the VAD speed increases above approximately 4000 RPM, the λVAD values diverge, demonstrating the direct relationship with Emax: having a peak of approximately 0.8 for the greatest ventricular contractility (Emax = 2.0). As speed increases further and approaches 8000 RPM, the values of λVAD once again converge. Another discriminating feature is the location (speed) of the local maximum (“hump”) in the curves within the range of 4000 and 6000 RPM, with the peak occurring at increasing speeds for increasing contractility. The cause of the hump is due to the cooperative relationship of the VAD and native ventricle, precisely the point of the aortic valve opening, allowing forward flow. At the lowest speeds, there is a slight negative flow through the VAD and, thus, a more subdued λVAD. Conclusion: This simulation study shows that the Power Factor of VAD flow rate has the potential as a noninvasive surrogate measure of ventricular recovery that can be monitored continuously. The metric is sensitive to the interaction between the native left ventricle and the VAD and thus helpful in developing feedback control that optimizes cardiac rehabilitation.Figure 1. Simulation results for the Power Factor of VAD Flow Rate as a function of different VAD Speeds (RPM).

In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns.

Thromboembolic events remain a common complication for left ventricular assist device (LVAD) patients. To prevent in-pump thrombosis, third-generation LVADs use speed modulation, which is not synchronized with the native left ventricle (LV) contractility. This study aims to investigate the effect of speed modulation on intraventricular flow patterns, and specifically, the impact of timing relative to pressure variations in the LV. Stereo-particle image velocimetry measurements were performed in a patient-derived LV implanted with an LVAD, for different timings of the speed modulation and speed. Speed modulation has a strong effect on instantaneous afterload and flowrate (-16% and +20%). The different timings of the speed modulation resulted in different flowrate waveforms, exhibiting different maxima (5.3-5.9 L/min, at constant average flowrate). Moreover, the timing of the speed modulation was found to strongly influence intraventricular flow patterns, specifically, stagnation areas within the LV. These experiments highlight, once more, the complex relationship between LVAD speed, hemodynamic resistance, and intraventricular pressure. Overall, this study demonstrates the importance of considering native LV contractility in future LVAD controls, to improve hemocompatibility and reduce the risk of thromboembolic complications.

CARD19: In vitro and In vivo Testing of the Pulsatile CorWave Membrane LVAD

Background: Lack of physiologic pulsatility with the use of continuous flow (CF) LVADs has been associated with serious adverse events including stroke, bleeding, and aortic insufficiency. CorWave is developing a unique LVAD employing an undulating membrane to generate a physiologic pulse while improving hemocompatibility. The present studies focused on in vitro and in vivo testing of the pump control algorithms for hemodynamic performance and hemocompatibility. Methods: The pump actuator, membrane, and blood flow path were designed using respectively electromagnetic simulations (MAGNET), Fluid-Structure Interaction (COMSOL), and Computational Fluid Dynamics. Algorithms were developed for actuator control, synchronization with the native left ventricle (LV), suction detection, and adaptive physiologic control. They were tested in a mock circulation loop (MCL) with INTERMACS 1-2, 3-4, and 5-6 heart failure (HF) profiles using LV pressure-volume loops to examine performance. The algorithms were then tested in chronic implants in healthy sheep for up to 3 months, and in acute implants in sheep with induced HF (ejection fraction < 40%). Results: During MCL tests, in synchronous pulsation (SynchPuls) mode, the membrane pump generated a more physiologic PV loop, with lower mean left atrial pressures (LAP), increased native LV stroke volume, and 1:1 opening of the aortic valve. CF pumps generated a characteristic, non-physiologic narrow PV loop with elevated mean LAP and aortic valve opening once per 3-5 beats. These results demonstrated the SynchPuls algorithm could respond to changes in pre-load to better unload the LV, restore more physiologic hemodynamics, and ensure aortic valve opening, so we proceeded to animal trials, which present more dynamic and challenging conditions. During acute implants in sheep with HF, using SynchPuls, the membrane pump increased cardiac output from ~2 to ~4 LPM. The physiologic control algorithm adjusted pump output to prevent LV suction and retrograde flow during hemodynamic manipulations, including epinephrine administration, and head up or down tilt. The algorithms switched to continuous mode, as intended, when arrhythmias or tachycardia were detected. In chronic implants, the SynchPuls algorithm successfully synchronized with the LV for > 97% of heartbeats and adapted to circadian cycles. Biomarkers of end-organ function returned to baseline within 2 weeks of implant, hemolysis was < 20 mg/dL, and VWF activity was preserved during the chronic implants. Conclusion: These studies showed that the membrane pump can provide physiologic pulsatility and restore cardiac output in HF models. The algorithms’ robustness was confirmed in chronic implants. Overall, these successful tests demonstrated that the CorWave membrane pump can deliver the hemocompatibility, pulsatility, and adaptability required to advance the LVAD field.

The CorWave LVAD - Synchronized Pulsatility with Improved Hemodynamics

<h3>Purpose</h3> The CorWave LVAD employs a novel wave membrane technology to generate low shear blood propulsion that can produce a physiologic pulse. Herein, we report the results of in vitro and in vivo testing of pumps for hemodynamics, hemocompatibility, and durability. <h3>Methods</h3> Computational simulations were used to optimize shear stress in the blood flow path < 9 dyn/cm², the maximum that occurs in normal physiology, while improving hydraulic performance. Prototype pumps confirmed the hydraulic and hemocompatibility results with the optimized flow paths. Pulsatility control algorithms were tested for sensorless synchronization with the native left ventricle (LV), arrhythmia detection, and pulse pressure (PP) amplitude generation in 3 settings: 1) In vitro mock circulation loops (MCLs), 2) acute implants in sheep with induced heart failure (HF), and 3) chronic implants in healthy sheep. An adaptive pump control program was developed to adjust the pump operating settings in response to changes in pre-load or after-load. Pump durability was assessed by continuous operation in MCLs. <h3>Results</h3> During implants in sheep with HF (EF 20-40%), the cardiac output increased from a baseline of 2-3 LPM to 5-6 LPM with the CorWave LVAD operating in continuous and pulsatile modes. The pulsatility algorithm successfully synchronized to > 95% of LV contractions during acute and chronic implants without the use of sensors. The algorithm identified arrhythmia conditions for safe transitions to non-synchronized operating modes. CorWave pumps generated PPs > 30 mmHg in vitro, and > 25 mmHg in vivo, where PP was constrained due to limitations of the animal model. In vivo, the adaptive pump control program successfully adjusted the pump operating points in response to hemodynamic challenges. The pump hemocompatibility was confirmed by low hemolysis and preservation of von Willebrand Factor function during chronic implants. Three pumps have completed 1 year durability tests, with 7 additional devices running beyond 6 months. We are building lifecycle test stands to commence multiple year durability tests to support clinical trial submissions. <h3>Conclusion</h3> The CorWave LVAD has achieved milestones for pulsatile hemodynamic performance, hemocompatibility, and durability, demonstrating substantial progress towards clinical readiness, providing a credible alternative to rotary blood pumps.

A Mechanistic Lumped Parameter Model of the Berlin Heart EXCOR to Analyze Device Performance and Physiologic Interactions.

The Berlin Heart EXCOR (BH) is the only FDA-approved, extracorporeal pulsatile ventricular assist device (VAD) for infants and children with heart failure. Clinicians control four settings on the device-systolic and diastolic drive pressures, device pump rate, and systolic time as a percentage of the pump cycle. However, interactions between BH pneumatics and the native circulation remain poorly understood. Thus, establishing appropriate device size and settings can be challenging on a patient-to-patient basis. In this study we develop a novel lumped parameter network based on simplified device mechanics. We perform parametric studies to characterize device behavior, study interactions between the left ventricle (LV) and BH across different device settings, and develop patient-specific simulations. We then simulate the impact of changing device parameters for each of three patients. Increasing systolic pressure and systolic time increased device output. We identified previously unobserved cycle-to-cycle variations in LV-BH interactions that may impact patient health. Patient-specific simulations demonstrated the model's ability to replicate BH performance, captured trends in LV behavior after device implantation, and emphasized the importance of device rate and volume in optimizing BH efficiency. We present a novel, mechanistic model that can be readily adjusted to study a wide range of device settings and clinical scenarios. Physiologic interactions between the BH and the native LV produced large variability in cardiac loading. Our findings showed that operating the BH at a device rate greater than the patient's native heart decreases variability in physiological interactions between the BH and LV, increasing cardiac offloading while maintaining cardiac output. Device rates that are close to the resting heart rate may result in unfavorable cardiac loading conditions. Our work demonstrates the utility of our model to investigate BH performance for patient-specific physiologies.

Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation.

BackgroundDysfunction and inflammation of hearts subjected to cold ischemic preservation may differ between left and right ventricles, suggesting distinct strategies for amelioration.Methods and ResultsExplanted murine hearts subjected to cold ischemia for 0, 4, or 8 h in preservation solution were assessed for function during 60 min of warm perfusion and then analyzed for cell death and inflammation by immunohistochemistry and western blotting and total RNA sequencing. Increased cold ischemic times led to greater left ventricle (LV) dysfunction compared to right ventricle (RV). The LV experienced greater cell death assessed by TUNEL+ cells and cleaved caspase‐3 expression (n = 4). While IL‐6 protein levels were upregulated in both LV and RV, IL‐1β, TNFα, IL‐10, and MyD88 were disproportionately increased in the LV. Inflammasome components (NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3), adaptor molecule apoptosis‐associated speck‐like protein containing a CARD (ASC), cleaved caspase‐1) and products (cleaved IL‐1β and gasdermin D) were also more upregulated in the LV. Pathway analysis of RNA sequencing showed increased signaling related to tumor necrosis factor, interferon, and innate immunity with ex‐vivo ischemia, but no significant differences were found between the LV and RV. Human donor hearts showed comparable inflammatory responses to cold ischemia with greater LV increases of TNFα, IL‐10, and inflammasomes (n = 3).ConclusionsMouse hearts subjected to cold ischemia showed time‐dependent contractile dysfunction and increased cell death, inflammatory cytokine expression and inflammasome expression that are greater in the LV than RV. However, IL‐6 protein elevations and altered transcriptional profiles were similar in both ventricles. Similar changes are observed in human hearts.

Left atrial assist device function at various heart rates using a mock circulation loop.

We are developing a new left atrial assist device (LAAD) for patients who have heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the hemodynamic effects of the LAAD under both normal heart conditions and various diastolic heart failure (DHF) conditions using a mock circulatory loop. A continuous-flow pump that simulates LAAD, was placed between the left atrial (LA) reservoir and a pneumatic ventricle that simulated a native left ventricle on a pulsatile mock loop. Normal heart (NH) and mild, moderate, and severe DHF conditions were simulated by adjusting the diastolic drive pressures of the pneumatic ventricle. With the LAAD running at 3200 rpm, data were collected at 60, 80, and 120 bpm of the pneumatic ventricle. Cardiac output (CO), mean aortic pressure (AoP), and mean LA pressure (LAP) were compared to evaluate the LAAD performance. With LAAD support, the CO and AoP rose to a sufficient level at all heart rates and DHF conditions (CO; 3.4-3.8 L/min, AoP; 90-105 mm Hg). Each difference in the CO and the AoP among various heart rates was minuscule compared with non-pump support. The LAP decreased from 21-23 to 17-19 mm Hg in all DHF conditions (difference not significant). Furthermore, hemodynamic parameters improved for all DHF conditions, independent of heart rate. The LAAD can provide adequate flow to maintain the circulation status at various heart rates in an in vitro mock circulatory loop.

Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices.

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.

The determinants of functional capacity in left ventricular assist device patients: many actors with not well defined roles.

: Improvement in hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs). However, functional capacity assessed by cardiopulmonary exercise test (CPET), following LVAD implantation, remains considerably restricted. In this review, we analyzed the current knowledge on the causes of the persistent limitation in exercise capacity in CF-LVAD patients. Limitation to exercise is multifactorial and involves: LVAD factors (fixed CF-LVAD pump speed), native cardiac factors (residual function of native left ventricle, right ventricular dysfunction, aortic valve abnormalities), comorbidities (abnormal skeletal muscle metabolism, low skeletal muscle mass, anemia), patient's characteristics (age, physical deconditioning). In addition, we emphasize the role of some potential therapeutic strategies like the increase in CF-LVAD pump speed according to the patient's activity, the echo-optimization of the device (paying attention to right ventricular function and aortic valve opening), the implementation of physical rehabilitation and the treatment of potentially reversible extracardiac factors (anemia, muscle deconditioning, obesity).

Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction

Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n = 15) or ESA (6 μg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.

Mechanical Circulatory Support for Biventricular Heart Failure Using Continuous-Flow Total Artificial Heart

Purpose Biventricular assist device (BVAD) implantation is the treatment of choice in patients with severe biventricular heart failure (BHF) and cardiogenic shock . We previously developed a miniaturized continuous flow double-ended centrifugal pump intended for total artificial heart implant (CFTAH). The purpose of this initial in vitro study was to prove that scaled down CFTAH can be suitable for biventricular support. Methods The CFTAH was tested in BVAD configuration at 2 pump speeds (4500 and 6000 rpm) on a pulsatile mock loop with two pneumatic ventricles that simulated normal and heart failure conditions (moderate and severe) by adjusting the systolic and diastolic drive pressures to simulate hemodynamics of the failing biventricular function. Results The BVAD performance was maintained very well for both atrial and ventricular cannulation within the 4500 - 6000 rpm range. A stable hemodynamics were maintained, and the pump's self-regulating performance was confirmed with the most of atrial pressure difference (LAP-RAP) falling within ±5-15 mm Hg in (Mod.) and severe (Sev.) right (RHF) and left HF (LHF) conditions. Left and right pump flows (LPF and RPF) and total flow (TF) increased as the BVAD speed was increased (Figure). The TF was higher than LPF and RPF due to output from the native ventricles, and the LPF was higher than RPF with pump speed of 6,000 rpm, but the TF appeared balanced due to larger native right ventricular output vs. native left ventricle with given condition. Conclusion These initial in vitro study demonstrated that use of the CFTAH as BVAD supports cardiac output and arterial pressure in BHF conditions. In vivo evaluation of this technology is currently pending.

Blood damage in Left Ventricular Assist Devices: Pump thrombosis or system thrombosis?

Despite significant technical advancements in the design and manufacture of Left Ventricular Assist Devices, post-implant thrombotic and thromboembolic complications continue to affect long-term outcomes. Previous efforts, aimed at optimizing pump design as a means of reducing supraphysiologic shear stresses generated within the pump and associated prothrombotic shear-mediated platelet injury, have only partially altered the device hemocompatibility. We examined hemodynamic mechanisms that synergize with hypershear within the pump to contribute to the thrombogenic potential of the overall Left Ventricular Assist Device system. Numerical simulations of blood flow in differing regions of the Left Ventricular Assist Device system, that is the diseased native left ventricle, the pump inflow cannula, the impeller, the outflow graft and the anastomosed downstream aorta, reveal that prothrombotic hemodynamic conditions might occur at these specific sites. Furthermore, we show that beyond hypershear, additional hemodynamic abnormalities exist within the pump, which may elicit platelet activation, such as recirculation zones and stagnant platelet trajectories. We also provide evidences that particular Left Ventricular Assist Device implantation configurations and specific post-implant patient management strategies, such as those allowing aortic valve opening, are more hemodynamically favorable and reduce the thrombotic risk. We extend the perspective of pump thrombosis secondary to the supraphysiologic shear stress environment of the pump to one of Left Ventricular Assist Device system thrombosis, raising the importance of comprehensive characterization of the different prothrombotic risk factors of the total system as the target to achieve enhanced hemocompatibility and improved clinical outcomes.

Esmolol Corrects Severe Hypoxemia in Patients with Femoro-Femoral Venoarterial Extracorporeal Life Support for Lung Transplantation

Competitive flows syndrome result in severe regional hypoxemia when the deoxygenated flow from the native left ventricle (LV) competes with oxygenated flow from extracorporeal life support (ECLS) pump with potentially severe consequences for the cerebral and coronary circulations. Fast correction of hypoxemia could be obtained by decreasing native LV flow by infusion of a short-acting beta-blocker (esmolol). Our purpose was to retrospectively review the efficacy of esmolol in this situation and hypothesize on the potential mechanisms of action and the associated risks. This is a retrospective analysis of five clinical cases, who underwent lung transplantation and a femoro-femoral venoarterial (VA) ECLS. The patients presented severe hypoxemia (SpO2&lt; 85%) measured through photoplethysmography on a right hand finger. From the patients' medical records and anesthesia flowcharts, hemodynamic, right heart catheterization, echocardiography variables, and arterial blood gas results were noted before and after injection of esmolol. Mechanical ventilation and VA ECLS function variables were optimized and unchanged before and after esmolol injection. All patients had terminal respiratory failure with pulmonary hypertension and conserved LV systolic function. Immediately following esmolol injection (1.3 ± .7 mg/kg; mean ± 1 SD), SpO2increased from 73% ± 12 to 95% ± 6; blood to arterial partial pressure in CO2(PaCO2) decreased from 52 ± 18 to 35 ± 7 mmHg systolic pulmonary artery pressure decreased from 61 ± 8 to 50 ± 12 mmHg; the pulmonary artery oxygen saturation (SvO2); increased from 51% ± 24 to 77% ± 12; systemic arterial pressure or catecholamine requirements were unchanged. In conclusion, these results suggest that injection of esmolol allowed rapid correction of regional hypoxemia occurring during lung transplantation despite femoro-femoral VA ECLS. The mechanism is probably a decreased cardiac output of the native LV due to esmolol-induced negative inotropic and chronotropic effects without significant adverse effects on systemic tissue perfusion.

Control system design for the mock ventricle with aortic and mitral valve resistance uncertainty

Reproducing the native left ventricle’s contractile behavior is the key ingredient for the mock cardiovascular circulatory system. It can be achieved by controlling either mock ventricle’s pressure or volume so that it could follow the reference signal calculated by the Elastance waveform. However, due to inherent uncertainties of the parameter values of the mock ventricle, such as check valve resistance, it is difficult to achieve high quality control performance. In this paper, we present an adaptive control scheme to overcome this parameter value uncertainty and to achieve high quality control performance. To the best knowledge of the author, it is the first report that reproduces the mock ventricle pumping dynamics precisely considering the resistance of the aortic/mitral check valves and overcoming the uncertainty of them. In the paper, along with the detailed design of the controller, rigorous proof of the stability and the convergence is presented as well. Computer simulation was performed using an electrical-analog cardiovascular circulatory system model and a piston pump mock ventricle model. Results confirmed that adaptive control achieved almost perfect tracking performance in spite of large parameter uncertainty and high bandwidth dynamic characteristics of the mock ventricle. Performance comparison verified the superiority of the adaptive controller over PID controllers.

Systemic perfusion at peak incremental exercise in left ventricular assist device recipients: Partitioning pump and native left ventricle relative contribution

BackgroundIn continuous-flow left ventricular assist device (LVAD) recipients, little is known about the relative pump- and left ventricle-generated blood flow (PBF and LVBF, respectively) contribution to peak systemic perfusion during incremental exercise and about how PBF/LVBF interplay and exercise capacity may be affected by pump speed increase. MethodsTwenty-two LVAD recipients underwent ramp cardiopulmonary exercise tests at fixed and increasing pump speed (+ 1.5% of baseline speed/10 W workload increase), echocardiography and NT-proBNP dosage. Peak systemic perfusion was peak VO2/estimated peak arterio-venous O2 difference, and LVBF was systemic perfusion minus PBF provided by LVAD controller. A change of peak percentage of predicted VO2max (Δpeak%VO2) ≥ 3 in increasing- vs. fixed-speed test was considered significant. ResultsTricuspid annular plane systolic excursion (TAPSE) and NT-proBNP were significantly lower and higher, respectively, in Δpeak%VO2 < 3 than ≥ 3. A LVBF contribution to systemic perfusion significantly larger than that of PBF was observed in Δpeak%VO2 ≥ 3 vs. < 3 in fixed-speed test, which was further amplified in increasing-speed test (2.4 ± 1.7 l/min vs. 2.0 ± 1.5 l/min and 0.8 ± 2.2 l/min vs. 1.3 ± 2.3 l/min, respectively, p for trend < 0.0005). Among several clinical-instrumental parameters, logistic regression selected only TAPSE > 13 mm as a predictor of Δpeak%VO2 ≥ 3. ConclusionsA significant LVBF contribution to peak systemic perfusion and pump speed increase-induced peak VO2 improvement was detectable only in patients with a more preserved right ventricular systolic function and stable hemodynamic picture. These findings should be taken into consideration when designing LVAD controllers aiming to increase pump speed according to increasing exercise demands.

Reverse Remodeling With Left Ventricular Assist Devices

Over the last 2 decades, numerous advancements in medical therapies have improved patient outcomes in heart failure (HF). However, a significant number of patients still progress to end-stage HF, in which treatment options are largely limited to cardiac transplantation. As patient demands for transplant continue to exceed the supply of available organs, mechanical assist devices—specifically, the left ventricular assist device (LVAD)—were initially introduced as a bridge to cardiac transplantation. LVADs have 2 important beneficial effects. First, LVADs are placed in parallel to the native left ventricle (LV), causing pressure and volume unloading of the LV. Second, LVADs restore cardiac output and subsequent perfusion to the organs. As a result of these 2 effects, it became evident that some patients had actual improvement in LV function after LVAD placement. The term reverse remodeling was used to describe the improvement in myocardial function that was observed in patients with a seemingly end-stage disease. With reverse remodeling, a new hope for the treatment of HF was born—using LVADs as a bridge to recovery; however, to date, this promise has largely been unrealized. This probably is reflective of the fact that the sequela of mechanical ventricular unloading are quite complex and appear to involve the engagement of competing biological pathways including regression of cardiomyocyte hypertrophy as well as progressive cell atrophy. Although the promise of ventricular recovery still persists, its actualization will await a more comprehensive dissection of these competing biological processes. This review will discuss the beneficial clinical effects of LVAD support as well as review what is known about the cellular and molecular response to mechanical unloading and mechanisms of reverse remodeling. Key research findings have been summarized in the Table. View this table: Table. Summary of Research of LVAD Support on Clinical Effects and the Cellular and Molecular Changes That May Contribute to Reverse …

Design Concepts and Principle of Operation of the HeartWare Ventricular Assist System

Implantable left ventricular assist devices provide circulatory support for patients at risk of death from refractory, end-stage heart failure. Rotary blood pumps have been designed for increased reliability and smaller size for use in a broader population of patients than the first-generation pulsatile devices. The design concepts and principle of operation of the HeartWare System are discussed. The HeartWare Ventricular Assist System (HVAD) is a small centrifugal flow pump with a displacement volume of 50 ml and an output capacity of 10 L/min. A unique wide-blade impeller is suspended by hybrid passive magnets and hydrodynamic forces. An integrated inflow cannula is inserted into the left ventricle and is held in position by an adjustable sewing ring; the pump is positioned in the pericardial space. The 10-mm outflow graft is anastomosed to the ascending aorta. External system components include the microprocessor-based controller, a monitor, lithium-ion battery packs, alternating current and direct current power adapters, and a battery charger. Physiologic control algorithms are incorporated for safe operation. Preclinical life cycle tests have shown the HVAD to be highly reliable. This system design offers reliability, portability, and ease of use for ambulatory patients.

Modeling, analysis, and validation of a pneumatically driven left ventricle for use in mock circulatory systems

In this work a pneumatically driven mock left ventricle and a native left ventricle are modeled and alternatively connected to the numerical model of a closed circulatory system comprising the systemic circulation, the left atrium, and inlet and outlet ventricular valves. By simulating physiological changes of the system working conditions, behavior and preload sensitivity of the pneumatic ventricle have been compared to those of a native ventricle. Results show that a pneumatic ventricle, when used as a fluid actuator in mock circulations, has low flexibility in reproducing different scenarios, its interaction with peripheral circulatory districts is characterized by non-physiological values, and its preload sensitivity is in poor agreement with physiological data. Results’ analysis also shows that present mock circulatory systems for testing cardiovascular prostheses are inadequate, if a careful attention is not paid to the pumping action of the pneumatic ventricle. The presented computer model, validated by comparing numerical results with in vitro measurements available in the literature, can be used for designing in vitro experiments, while choosing the best control strategy for pneumatic systems.