Search

Background: Left ventricular assist devices (LVADs) have been used as a standard treatment option for patients with advanced heart failure. However, these devices are prone to adverse events. Nonsurgical bleeding (NSB) is the most common complication in patients with continuous flow (CF) LVADs. The development of acquired von Willebrand syndrome (AVWS) in CF-LVAD recipients is thought to be a key factor. However, AVWS is seen across a majority of LVAD patients, not just those with NSB. The purpose of this study was to examine the link between acquired platelet defects and NSB in CF-LVAD patients., Methods: Blood samples were collected from 62 CF-LVAD patients at pre- and 4 post-implantation timepoints. Reduced adhesion receptor expression (GPIbα and GPVI) and activation of platelets (GPIIb/IIIa activation) were used as markers for acquired platelet defects., Results: Twenty-three patients experienced at least one NSB episode. Significantly higher levels of platelet activation and receptor reduction were seen in the postimplantation blood samples from bleeders compared with non-bleeders. All patients experienced the loss of high molecular weight monomers (HMWM) of von Willebrand Factor (vWF), but no difference was seen between the two groups. Multivariable logistic regression showed that biomarkers for reduced platelet receptor expression (GPIbα and GPVI) and activation (GPIIb/IIIa) have more predictive power for NSB, with the area under curve (AUC) values of 0.72, 0.68, and 0.62, respectively, than the loss of HMWM of vWF (AUC: 0.57)., Conclusion: The data from this study indicated that the severity of acquired platelet defects has a direct link to NSB in CF-LVAD recipients., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Nonsurgical bleeding (NSB) in heart failure (HF) patients with continuous-flow left ventricular assist device (CF-LVAD) support is the most common clinical complication. The aim of this study was to investigate the association between oxidative stress and platelet glycoproteins GPIbα and GPVI shedding on the incidence of NSB in CF-LVAD patients. Fifty-one HF patients undergoing CF-LVAD implantation and 11 healthy volunteers were recruited. Fourteen patients developed NSB (bleeder group) during 1 month follow-up duration, while others were considered nonbleeder group (n = 37). Several biomarkers of oxidative stress were quantified at baseline and weekly intervals in all patients. Surface expression and plasma elements of platelet receptor glycoproteins GPIbα and GPVI were measured. Oxidative stress biomarkers and platelet GPIbα and GPVI receptor-shedding (decreased surface expression and higher plasma levels) were found to be preexisting conditions in baseline samples of both groups of HF patients when compared with healthy volunteers. Significantly elevated oxidative stress biomarkers and platelet glycoprotein receptor shedding were observed in postimplant bleeder group temporarily when compared with nonbleeder group. Strong significant associations between biomarkers of oxidative stress and platelet glycoprotein receptor shedding were observed, suggesting a possible role of oxidative stress in platelet integrin shedding leading to NSB in CF-LVAD patients. Receiver operating characteristic analyses of GPIbα and GPVI indicated that the likelihood of NSB had a predictive power of bleeding complication in CF-LVAD patients. In conclusion, elevated oxidative stress may play a role in GPIbα and GPVI shedding in the event of NSB. Thus, oxidative stress and GPIbα and GPVI shedding may be used as potential biomarkers for bleeding risk stratification in those patients.

Introduction: Oxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs)., Materials and Methods: We recruited 47patients implanted with CF-LVADs and 15 healthy volunteers. Fourteen patients developed MBC (bleeder group) within one month after implantation while others were considered non-bleeder group (n=33). Oxidative stresses were evaluated by measuring reactive oxygen species (ROS) in platelets, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) and oxidized low density lipoprotein (oxLDL). Assessments of α2bβ3 were carried out using flow cytometry and ELISA., Results: Biomarkers of oxidative stress and α2bβ3 shedding (decreased surface expression and higher plasma levels) were found to be preexisting condition in all HF patients prior to CF-LVAD implantation compared to the healthy volunteers. Significantly elevated levels of ROS and oxLDL; concomitant depletion of SOD and TAC; and α2bβ3 shedding were observed in the bleeder group temporarily in comparison to the non-bleeder group after CF-LVAD implantation. A significantly strong association between α2bβ3 shedding and biomarkers of oxidative stress was observed; suggesting a potential role of oxidative stress in platelet integrin shedding leading to MBC after CF-LVAD implantation. Moreover, a receiver operating characteristic (ROC) analysis indicated that the likelihood of MBC data from Integrin α2bβ3 shedding had a predictive power of MBC in CF-LVAD patients., Conclusions: Oxidative stress might play a potential role in accelerating α2bβ3 shedding and platelet dysfunction, resulting in MBC in CF-LVAD patients. Integrin α2bβ3 shedding may be used to refine bleeding risk stratification in CF-LVAD patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference). Production of reactive oxygen species (ROS) in platelets, total antioxidant capacity (TAC), oxidized low-density lipoproteins (oxLDL), expression of Bcl-2 and Bcl-xL, Bax and release of cytochrome c (Cyt.c), platelet mitochondrial membrane potential (Δψ m ), activation of caspases, gelsolin cleavage and platelet apoptosis were examined. Significantly elevated ROS, oxLDL and depleted TAC were evident in the bleeder group compared to non-bleeder group (p < 0.05). Platelet pro-survival proteins (Bcl-2, Bcl-xL) were significantly reduced in the bleeder group in comparison to the non-bleeder group (p < 0.05). Translocation of Bax into platelet mitochondria membrane and subsequent release of Cyt.c were more prevalent in the bleeder group. Platelet mitochondrial damage, activation of caspases, gelsolin cleavage, and ultimate platelet apoptosis in the bleeder group were observed. Oxidative stress and activation of both intrinsic and extrinsic pathways of platelet apoptosis may be linked to NSB in CF-LVAD patients. Additionally, biomarkers of oxidative stress, examination of pro-survivals and pro-apoptotic proteins in platelets, mitochondrial damage, caspase activation, and platelet apoptosis may be used to help identify HF patients at high risk of NSB post-implant.

Continuous-flow left ventricular assist devices (CF LVADs) are rotary blood pumps that improve mean blood flow, but with potential limitations of non-physiological ventricular volume unloading and diminished vascular pulsatility. In this study, we tested the hypothesis that left ventricular unloading with increasing CF LVAD flow increases myocardial flow normalized to left ventricular work. Healthy (n = 8) and chronic ischemic heart failure (IHF, n = 7) calves were implanted with CF LVADs. Acute hemodynamics and regional myocardial blood flow were measured during baseline (LVAD off, clamped), partial (2-4 L/min) and full (>4 L/min) LVAD support. IHF calves demonstrated greater reduction of cardiac energy demand with increasing LVAD support compared to healthy calves, as calculated by rate-pressure product. Coronary artery flows (p < 0.05) and myocardial blood flow (left ventricle (LV) epicardium and myocardium, p < 0.05) decreased with increasing LVAD support in normal calves. In the IHF model, blood flow to the septum, LV, LV epicardium, and LV myocardium increased significantly with increasing LVAD support when normalized to cardiac energy demand (p < 0.05). In conclusion, myocardial blood flow relative to cardiac demand significantly increased in IHF calves, thereby demonstrating that CF LVAD unloading effectively improves cardiac supply and demand ratio in the setting of ischemic heart failure.

The objective of this study was to investigate the changes in oxidative stress (OS) and circulating regulatory T cells (Tregs) of the immune system in patients supported by continuous-flow ventricular assist device (CF-VAD) with or without infection. We recruited 16 CF-VAD patients (5 with infection and 11 without infection) and 7 healthy volunteers. Generation of reactive oxygen species (ROS) from lymphocytes, superoxide dismutase (SOD) in erythrocyte, total antioxidant capacity (TAC), and oxidized low-density lipoprotein (oxLDL) in plasma were measured. Circulating Tregs were evaluated by flow cytometry. Heart failure (HF) patients had elevated OS than healthy volunteers as evident from higher lymphocyte ROS, elevated oxLDL, as well as depleted SOD and TAC levels. At baseline, HF patients had decreased percentage of Tregs (5.12 ± 1.5% vs. 8.14 ± 3.01%, p < 0.01) when compared with healthy volunteers. Postimplant patients with infection illustrated 35% and 44% rise in ROS and oxLDL, respectively, 31% decrease in TAC, and marked rise in percentage of Tregs (14.27 ± 3.17% vs. 9.38 ± 3.41%, p < 0.01) when compared with the patients without infection. Elevated OS and rise in Tregs were more prominent in CF-VAD patients with infection. In conclusion, OS and compromised immune system may be important indicators of systemic response of the body to CF-VAD among HF patients with infection.

Counterpulsation devices (CPDs) require an accurate, reliable electrocardiogram (ECG) waveform for triggering inflation and deflation. Surface electrodes are for short-term use, and transvenous/epicardial leads require invasive implant procedure. A subcutaneous ECG lead configuration was developed as an alternative approach for long-term use with timing mechanical circulatory support (MCS) devices. In this study, efficacy testing was completed by simultaneously recording ECG waveforms from clinical-grade epicardial (control) and subcutaneous (test) leads in chronic ischemic heart failure calves implanted with CPD for up to 30 days. Sensitivity and specificity of CPD triggering by R-wave detection was quantified for each lead configuration. The subcutaneous leads provided 98.9% positive predictive value and 98.9% sensitivity compared to the epicardial ECG leads. Lead migration (n = 1) and fracture (n = 1) were observed in only 2 of 40 implanted leads, without adversely impacting triggering efficacy due to lead redundancy. These findings demonstrate the efficacy of subcutaneous ECG leads for long-term CPD timing and potential use as an alternative method for MCS device timing.

The role of oxidative stress and leukocyte activation has not been elucidated in developing systemic inflammatory response syndrome (SIRS) in heart failure (HF) patients after continuous-flow left ventricular assist device (CF-LVAD) implantation. The objective of this study was to investigate the change of plasma redox status and leukocyte activation in CF-LVAD implanted HF patients with or without SIRS. We recruited 31 CF-LVAD implanted HF patients (16 SIRS and 15 non-SIRS) and 11 healthy volunteers as the control. Pre- and postimplant blood samples were collected from the HF patients. Plasma levels of oxidized low-density lipoprotein (oxLDL), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) in erythrocyte, myeloperoxidase (MPO), and polymorphonuclear elastase (PMN-elastase) were measured. The HF patients had a preexisting condition of oxidative stress than healthy controls as evident from the higher oxLDL and MDA levels as well as depleted SOD and TAC. Leukocyte activation in terms of higher plasma MPO and PMN-elastase was also prominent in HF patients than controls. Persistent oxidative stress and reduced antioxidant status were found to be more belligerent in HF patients with SIRS after the implantation of CF-LVAD when compared with non-SIRS patients. Similar to oxidative stress, the activation of blood leukocyte was significantly highlighted in SIRS patients after implantation compared with non-SIRS. We identified that the plasma redox status and leukocyte activation became more prominent in CF-LVAD implanted HF patients who developed SIRS. Our findings suggest that plasma biomarkers of oxidative stress and leukocyte activation may be associated with the development of SIRS after CF-LVAD implant surgery., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: The objective of this study was to investigate the change of platelet function and platelet mitochondrial membrane potential in contentious-flow left ventricular assist device (CF-LVAD)-implanted heart failure (HF) patients with or without systemic inflammatory response syndrome (SIRS)., Methods and Results: We recruited 31 CF-LVAD patients (16 SIRS and 15 non-SIRS) and 11 healthy volunteers as control. Pre- and post-implantation blood samples were collected. We used PFA-100 to test platelet functionality. Mitochondrial potential-sensitive dye was used to detect platelet dysfunction (mitochondrial membrane potential; ΔΨm) via flow cytometry. The percentage of depolarized-ΔΨm platelets was found to be a preexisting condition in all HF patients before CF-LVAD implantation compared with control subjects (10.3 ± 6.3% vs 2.8 ± 2.2%; P < .001). As evident from the PFA-100 test, the HF patients who developed SIRS after CF-LVAD implantation had significantly more qualitative platelet defects and thrombocytopathies compared with baseline. After implantation, the depolarized platelets in the SIRS patients increased by 2-fold compared with baseline (18.2 ± 8.4% vs 9.0 ± 6.6%; P < .01); whereas no change was noticed in the non-SIRS patients (10.9 ± 6.2% vs 11.7 ± 5.8%; P = .75)., Conclusions: We identified that platelet function and mitochondrial damage were enhanced in CF-LVAD patients with SIRS. Our findings suggest that depolarization of mitochondrial membrane potential is associated with SIRS after CF-LVAD implantation surgery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Non-surgical bleeding (NSB) is the most common clinical complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the role of platelet functionality contributing to NSB after CF-LVAD implantation is crucial for prevention and management of this adverse event. The aim of this study was to examine the role of intraplatelet reactive oxygen species (ROS) and platelet damage on the incidence of bleeding events after CF-LVAD implantation in HF patients. We recruited 25 HF patients implanted with CF-LVADs and 11 healthy volunteers as the control. Intraplatelet ROS generation, platelet mitochondrial damage and platelet apoptosis were quantified by flow cytometry. Among 25 patients, 8 patients developed non-surgical bleeding within one month after CF-LVAD implantation. Intraplatelet ROS, depolarized and apoptotic platelet were found to be pre-existing conditions in all baseline samples of the 25 HF patients when compared to the healthy volunteers. There was no significant difference in the levels of ROS between the non-bleeder and the bleeder groups prior to CF-LVAD implantation, although we noticed 2-fold and 1.5-fold rise in depolarized and apoptotic platelets, respectively, in the bleeder group compared to those in the non-bleeder group. Post implant levels of intraplatelet ROS, depolarized and apoptotic platelets increased and remained elevated in the bleeder group, whereas periodic decreases were noticed in the non-bleeder group, suggesting the potential role of platelet damage on bleeding incidence. ROS generation after CF-LVAD implantation positively associated with platelet apoptosis (ρ = 0.4263, p = 0.0023) and depolarized platelets (ρ = 0.4774, p = 0.0002), especially the latter. In conclusion, elevated intraplatelet ROS and platelet damage may be linked to the NSB among HF patients supported by CF-LVAD. These results provide mechanistic insights into the bleeding complication in patients with CF-LVAD support.

Background: Non-surgical bleeding (NSB) is a major complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the hemostatic defects contributing to NSB after CF-LVAD implantation is crucial for prevention of this adverse event. The aim of this study was to examine the link between platelet glycoprotein Ibα (GPIbα) ectodomain shedding and NSB in CF-LVAD recipients and to identify a potential biomarker of NSB., Methods: Serial blood samples were collected from 35 HF patients supported with CF-LVADs. Platelet function was evaluated by a platelet function analysis device and thromboelastography (TEG). Platelet GPIbα shedding, von Willebrand factor (vWF) antigen and vWF collagen binding capacity were determined using enzyme-linked immunosorbent assays (ELISAs). The structural analysis of vWF was performed by gel electrophoresis. These platelet function measures with vWF parameters of the patients who had NSB between 4 and 32 days after CF-LVAD implantation (bleeder) were analyzed against those without NSB (non-bleeder). Blood samples from 7 healthy individuals were collected to obtain healthy reference values for the laboratory assays., Results: Elevated GPIbα shedding was found to be a pre-existing condition in all HF patients prior to CF-LVAD implantation. Post-operative level of GPIbα shedding increased and remained elevated in the bleeder group, whereas a consistent decrease was found in the non-bleeder group. A receiver operating characteristic (ROC) analysis indicated that the level of GPIbα shedding had a predictive power of NSB in patients on CF-LVAD support., Conclusions: Platelet GPIbα ectodomain shedding which attenuates platelet reactivity is associated with NSB. Plasma GPIbα level may potentially be used to refine bleeding risk stratification in CF-LVAD patients., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Modulation of pump speed has been proposed and implemented clinically to improve vascular pulsatility in continuous flow ventricular assist device patient. The flow dynamics of the HVAD with a promising asynchronous pump speed modulation and its potential risk for device-induced blood trauma was investigated numerically. The boundary conditions at the pump inlet and outlet were defined using the pressure waveforms adapted from the experimentally recorded ventricular and arterial pressure waveforms in a large animal ischemic heart failure (IHF) model supported by the HVAD operated at constant and modulated pump speeds. Shear stress fields and hemolysis indices were derived from the simulated flow fields. The overall features of the computationally generated flow waveforms at simulated constant and pulse-modulated speed operations matched with those of the experimentally recorded flow waveforms. The simulations showed that the shear stress field and hemolysis index vary throughout the cardiac cycle under the constant speed operation, and also as a function of modulation profile under modulated speed operation. The computational model did not demonstrate any differences in the time average hemolysis index between constant and modulated pump speed operations, thereby predicting pulse-modulated speed operation may help to restore vascular pulsatility without any further increased risk of blood trauma. Graphical abstract The streamline inside the HVAD pump and the wall shear stress distribution on the impeller surface at six discrete time instants over one cardiac cycle under constant speed operation (3000 rpm) (a) and under pulse-modulated speed operation (b). c Computationally predicted flow rate waveform under pulse-modulated speed operation. d Computationally predicted time-varying HI generated by the HVAD pump under the two operation modes constant speed (dash line) and pulse-modulated speed (solid line). These figures indicate that the pulse-modulated speed operation may help to restore vascular pulsatility without any further increased risk of blood trauma. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to demonstrate that short-term cardiac unloading with a left ventricular (LV) assist device (LVAD) after acute myocardial infarction (MI) can conserve calcium cycling and improve heart function. Background: Heart failure secondary to MI remains a major source of morbidity and mortality. Alterations in calcium cycling are linked to cardiac dysfunction in the failing heart. Methods: Adult Dorsett hybrid sheep underwent acute MI and were mechanically unloaded with an axial-flow LVAD (Impella 5.0) for 2 weeks (n = 6). Six sheep with MI only and 4 sham sheep were used as controls. All animals were followed for 12 weeks post-MI. Regional strains in the LV were measured by sonomicrometry. Major calcium-handling proteins (CHPs), including sarco-/endoplasmic reticulum calcium ATPase-2α (SERCA-2α), Na+-Ca2+ exchanger-1, and phospholamban, and Ca2+-ATPase activity were investigated. The electrophysiological calcium cycling in single isolated cardiomyocytes was measured with the patch-clamp technique. The related ultrastructures were studied with electron microscopy. Results: LVAD unloading alleviated LV dilation and improved global cardiac function and regional contractility compared with the MI group. The regional myocardial strain (stretch) was minimized during the unloading period and even attenuated compared with the MI group at 12 weeks. Impaired calcium cycling was evident in the adjacent noninfarcted zone in the MI group, whereas CHP expression was normalized and Ca2+-ATPase activity was preserved in the LVAD unloading group. The electrophysiological calcium cycling was also conserved, and the ultrastructural damage was ameliorated in the unloaded animals. Conclusions: Short-term LVAD unloading may conserve calcium cycling and improve heart function during the post-infarct period. [Copyright &y& Elsevier]

For the need for respiratory support for patients with acute or chronic lung diseases to be addressed, a novel integrated maglev pump-oxygenator (IMPO) is being developed as a respiratory assist device. IMPO was conceptualized to combine a magnetically levitated pump/rotor with uniquely configured hollow fiber membranes to create an assembly-free, ultracompact system. IMPO is a self-contained blood pump and oxygenator assembly to enable rapid deployment for patients requiring respiratory support or circulatory support. In this study, computational fluid dynamics (CFD) and computer-aided design were conducted to design and optimize the hemodynamics, gas transfer, and hemocompatibility performances of this novel device. In parallel, in vitro experiments including hydrodynamic, gas transfer, and hemolysis measurements were conducted to evaluate the performance of IMPO. Computational results from CFD analysis were compared with experimental data collected from in vitro evaluation of the IMPO. The CFD simulation demonstrated a well-behaved and streamlined flow field in the main components of this device. The results of hydrodynamic performance, oxygen transfer, and hemolysis predicted by computational simulation, along with the in vitro experimental data, indicate that this pump-lung device can provide the total respiratory need of an adult with lung failure, with a low hemolysis rate at the targeted operating condition. These detailed CFD designs and analyses can provide valuable guidance for further optimization of this IMPO for long-term use. [ABSTRACT FROM AUTHOR]

Objective: Progressive left ventricular remodeling after myocardial infarction has been viewed as an important contributor to progressive heart failure. The objective of this study was to investigate the relationship between myocardial apoptosis and strain during progressive cardiac remodeling. Methods: Before creation of an anterolateral left ventricular infarction by ligation of diagonal arteries, 16 sonomicrometry transducers were placed in the left ventricular free wall of 8 sheep to assess regional deformation in the infarct, adjacent, and normally perfused remote myocardial regions over 8 weeks'' duration. Hemodynamic, echocardiographic and sonomicrometric data were collected before infarction and then 30 minutes and 2, 6, and 8 weeks after infarction. At the end of the study, regional myocardial tissues were collected for apoptotic signaling proteins. Results: At terminal study, an increase in left ventricular end-diastolic pressure of 8.1 ± 0.1 mm Hg, a decrease in ejection fraction from 54.19% ± 5.68% to 30.55% ± 2.72%, and an end-diastolic volume increase of 46.08 ± 5.02 mL as compared with the preinfarct values were observed. The fractional contraction at terminal study correlated with the relative abundance of apoptotic protein expressions: cytochrome c (r 2 = 0.02, P < .05), mitochondrial Bax (r 2 = 0.27, P < .05), caspase-3 (r 2 = 0.31, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r 2 = 0.30, P < .05). These myocardial apoptotic activities also correlated with remodeling strain: cytochrome c (r 2 = 0.02, P < .05), mitochondrial Bax (r 2 = 0.28, P < .05), caspase-3 (r 2 = 0.43, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r 2 = 0.37, P < .05). Conclusion: Increase in regional remodeling strain led to an increase in myocardial apoptosis and regional contractile dysfunction in heart failure. [Copyright &y& Elsevier]

Background: Device availability of mechanical circulatory or respiratory support to the right heart has been limited. The purpose of this study was to investigate the effect of right heart unloading and respiratory support with a wearable integrated artificial pump-lung (APL). Methods: The APL device was placed surgically between the right atrium and pulmonary artery in 7 sheep. Anti-coagulation was performed with heparin infusion. The device's ability to unload the right ventricle (RV) was investigated by echocardiograms and right heart catheterization at different bypass flow rates. Hemodynamics and echocardiographic data were evaluated. APL flow and gas transfer rates were also measured at different device speeds. Results: Hemodynamics remained stable during APL support. There was no significant change in systemic blood pressure and cardiac index. Central venous pressure, RV pressure, RV end-diastolic dimension and RV ejection fraction were significantly decreased when APL device flow rate approached 2 liters/min. Linear regression showed significant correlative trends between the hemodynamic and cardiac indices and device speed. The oxygen transfer rate increased with device speed. The oxygen saturation from the APL outlet was fully saturated (>95%) during support. The impact of APL support on blood elements (plasma free hemoglobin and platelet activation) was minimal. Conclusions: APL device support significantly unloaded the RV with increasing device speed. The device also provided stable hemodynamics and respiratory support in terms of blood flow and oxygen transfer. The right heart unloading performance of this wearable device needs to be evaluated further in an animal model of right heart failure with long-term support. [ABSTRACT FROM AUTHOR]