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Cardiogenic shock (CS) often occurs in patients suffering from rapidly progressing end-stage heart failure or acute myocardial infarction. Mechanical circulatory support may be used for patients who do not respond to medication or revascularization to stabilize hemodynamics. Extracorporeal ventricular assist device (Extra-VAD) has been reported to be successful for patients with cardiogenic shock. This study aimed to evaluate the 30-day in-vivo performance and safety of a newly developed Extra-VAD with maglev centrifugal pump technology, MoyoAssist®.The study was conducted with 6 healthy ovine models, weighing 43.2 ~ 59.6 kg. Cannulation was performed with a 34 Fr venous cannula surgically connected to the left arterial appendage and a 24 Fr arterial cannula inserted into descending aorta. The pump flow rate was maintained at 2 ~ 3 L/min to provide sufficient cardiac support without suction. Activated clotting time was maintained within the range of 150 ~ 250 s.No device-related adverse events occurred throughout the study. Plasma-free hemoglobin results were within the acceptable range of ventricular assist device therapy (40 mg/dl). MGS01 had an anticoagulation management related bleeding event and was terminated on day 29. All other sheep's biochemical test results were stable. The autopsy showed no embolism or thrombus formation and no end-organ damage.This study demonstrated that the MoyoAssist® Extra-VAD is able to provide cardiac support effectively and safely and may provide a new alternative choice for patients with CS in China.

Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD’s performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.

Long-term using continuous flow ventricular assist devices could trigger complications associated with diminished pulsatility, such as valve insufficiency and gastrointestinal bleeding. One feasible solution is to produce pulsatile flow assist with speed regulation in continuous flow ventricular assist devices. A third-generation blood pump with pulsatile operation control algorithm was first characterized alone under pulsatile mode at various speeds, amplitudes, and waveforms. The pump was then incorporated in a Mock circulation system to evaluate in vitro hemodynamic effects when using continuous and different pulsatile operations. Pulsatility was evaluated by surplus hemodynamic energy. Results showed that pulsatile operations provided sufficient hemodynamic assistance and increased pulsatility of the circulatory system (53% increment), the mean aortic pressure (65% increment), and cardiac output (27% increment). The pulsatility of the system under pulsatile operation support was increased 147% compared with continuous operation support. The hemodynamic performance of pulsatile operations is susceptible to phase shifts, which could be a tacking angle for physiological control optimization. This study found third-generation blood pumps using different pulsatile operations for ventricular assistance promising.

It has been reported that long-term use of continuous-flow mechanical circulatory support devices (CF-MCSDs) may induce complications associated with diminished pulsatility. Pulsatile-flow mechanical circulatory support devices (PF-MCSDs) have the potential of overcoming these shortcomings with the advance of technology. In order to promote in-depth understanding of PF-MCSD technology and thus encourage future mechanical circulatory support device innovations, engineering perspectives of PF-MCSD systems, including mechanical designs, drive mechanisms, working principles, and implantation strategies, are reviewed in this article. Some emerging designs of PF-MCSDs are introduced, and possible elements for next-generation PF-MCSDs are identified.

Objective: In vitro performance verification of ventricular assist devices using a mock circulatory loop is a prominent step to guarantee the system responses and the device performance and safety before the in vivo tests and ultimately clinical trials. Methods: In this article, we performed a comprehensive literature research to establish a verification matrix consisting of 12 test cases, defined by a set of physiological parameters which are commonly used to characterize a physiological condition. The clinical hemodynamic indicators for defining successful mechanical support were used as the acceptance criteria. A mock circulatory loop was customized to simulate the test cases, and a full verification protocol was described in details. An example left ventricular assist device was incorporated in the loop to accomplish a standard ventricular assist device performance verification. Result: The test cases based on clinical data with sufficient safety margin represent our understanding in defining the extremes of operation. The mock circulatory loop was capable of generating the test conditions in the verification matrix and reproducing the Frank–Starling law of the native heart. The effect of the left ventricular assist device assistance (characterized by the total systemic flow, mean aortic pressure, and left atrial pressure) was well verified by the proposed protocol and acceptance criteria. Conclusion: To date, all left ventricular assist devices made in China have been evaluated according this protocol and some of them have entered the clinical trial stage. We are closely observing the clinical data in order to further improve the performance of the platform and encourage more advances in mechanical circulatory assist devices.

Hemolysis is a major concern in blood-circulating devices, which arises due to non-physiological stresses on red blood cells from ambient flow environment or moving mechanical structures. Computational fluid dynamics (CFD) and empirical hemolysis prediction models have been increasingly used for the design and optimization of blood-circulating devices. The commonly used power-law models for hemolysis prediction often use Reynolds stress to represent effective stress, tend to over-predict hemolysis and fail to capture trends of flow-related hemolysis. This study proposed a new power-law formulation for the numerical hemolysis prediction. The new formulation related hemolysis to the energy dissipation rate, which could be readily obtained from CFD simulations. The model constants were regressed from existing hemolysis data. The new formulation was tested for three benchmark cases and compared to conventional power-law models. The results showed that the new formulation improved prediction of hemolysis for a broad range of flow regimes. The deviations of the predicted hemolysis from experimental results were within one order, and better correlated with experimental results. This study confirmed that Reynolds stress is the main cause of over-prediction of hemolysis for conventional power-law models. Proportionally, the blood damage predicted with Reynolds stresses is more than one order higher than viscous stress, in terms of energy dissipation.

Objective: For ventricular assist devices utilizing levitation bearing technology, collision and wear of the rotor would occur if the bearing cannot resist disturbances from patient activities and vibration/shock impacts. The reliability of ventricular assist devices can be seriously affected, potentially impairing blood compatibility (e.g. thrombus generation) and threatening patient safety. In this article, we proposed a vibrational disturbance test protocol for ventricular assist devices. Methods: Two kinds of vibrational disturbances—translational and rotational—were defined and the disturbance levels determined as 6G and 10 rad/s per possible patient activity impact. A test platform was built according to the disturbance level requirements. Results: The test platform successfully generated the required disturbance. The vibration test evaluation criteria for ventricular assist device assistance (characterized by the pressure head, flow rate, and driving current waveform) were well verified. Conclusion: Compared with translational vibration, rotational vibration had a greater impact on the rotor. Accurate control of high-speed rotor is difficult because of the gyroscopic effect. As conventional random vibration tests cannot cover all risk situations, it is recommended that translational and rotational disturbance tests are carried out for levitation ventricular assist devices. We recommend that researchers and manufacturers pay attention to the vibrational impact of rotor-levitated ventricular assist devices.

The IntraVAD is a miniature intra-aortic ventricular assist device (VAD) designed to work in series with the compromised left ventricle. A reverse-rotation control (RRc) mode has been developed to increase myocardial perfusion and reduce ventricular volume. The RRc mode includes forward rotation in systole and reverse rotation in diastole, which requires the IntraVAD to periodically reverse its rotational direction in synchrony with the cardiac cycle. This periodic reversal leads to changes in pressure force over the impeller, which makes the entire system less stable. To eliminate the mechanical wear of a contact bearing and provide active control over the axial position of the rotor, a miniature magnetically levitated bearing (i.e., the PM-Coil module) composed of two concentric permanent magnetic (PM) rings and a pair of coils-one on each side-was proposed to provide passive radial and active axial rotor stabilization. In the early design stage, the numerical finite element method (FEM) was used to optimize the geometry of the brushless DC (BLDC) motor and the maglev module, but constructing a new model each time certain design parameters were adjusted required substantial computation time. Because the design criteria for the module had to be modified to account for the magnetic force produced by the motor and for the hemodynamic changes associated with pump operation, a simplified analytic expression was derived for the expected magnetic forces. Suitable bearings could then be designed capable of overcoming these forces without repeating the complicated FEM simulation for the motor. Using this method at the initial design stage can inform the design of the miniature maglev BLDC motor for the proposed pulsatile axial-flow VAD.

Background Differential hypoxia exists in peripheral venoarterial (VA) extracorporeal membrane oxygenation (ECMO) patients with compromised lungs, causing hypoxic damage to heart or brain. We proposed an Avalon Elite (Maquet, Rastatt, Germany) double lumen cannula-based hybrid ECMO to add a venovenous (VV) blood flow into the pulmonary circulation onto the existing VA ECMO circuit to increase oxygen saturation in the left ventricle and ascending aorta, mitigating heart/brain hypoxia. Methods This hybrid ECMO circuit consists of two cannulas (27F Avalon Elite double lumen cannula from the inferior vena cava to the superior vena cava to right atrium to inferior vena cava; 17F infusion cannula in femoral artery), a blood pump, and a gas exchanger. This hybrid ECMO circuit was tested in 7 adult sheep with simulated lung failure. Total ECMO blood flow (2.8 to 3.3 L/min) was split between VV and VA blood flow. The VV blood flow was adjusted from 0% to 50% of total ECMO flow by approximately 10% increments. Results In VA ECMO, simulated respiratory failure resulted in differential hypoxia (low oxygen level in left ventricle and high oxygen level in abdominal aorta). In hybrid ECMO, adding VV blood flow (10% to 50% of total ECMO flow) to the VA ECMO circuit progressively increased left ventricle blood oxygen saturation from 70% ± 8% at zero VV blood flow (pure VA ECMO) to 82% ± 6% at 300 mL/min VV blood flow, and 96% ± 6% at 1,700 mL/min VV blood flow. Conclusions The Avalon Elite double-lumen cannula-based hybrid ECMO circuit is a simple circuit that provides efficient performance and flexible VA/VV blood distribution. In this hybrid ECMO circuit, incremental VV blood flow (10% to 50%) progressively increased left ventricular blood oxygen level, ensuring adequate heart and brain oxygen supply.

A cavopulmonary assist device (CPAD) has been developed for failing Fontan support. This CPAD pumps blood from superior/inferior vena cavae (SVC/IVC) to pulmonary artery. In this study, we compared failing Fontan support with CPAD versus veno-arterial extracorporeal membrane oxygenation (VA ECMO) in silico. A numerical lumped-parameter circulatory system model was used to simulate Fontan circulation. Failing Fontan was simulated by increased pulmonary resistance. Central venous pressure (CVP), mean pulmonary arterial pressure (mPAP), left atrial pressure (LAP), and univentricular outflow (CO) were simulated and compared with published clinical data. The CPAD and VA ECMO were simulated using 1-5 L/min pump flows. In agreement with published clinical data, the simulated failing Fontan condition had increased CVP (19 mmHg) and mPAP (18 mmHg) with decreased LAP (7 mmHg) and cardiac output (3 L/min) compared with functional Fontan condition. The CPAD achieved total Fontan assistance with pump flows higher than original CO. Veno-arterial extracorporeal membrane oxygenation provided partial Fontan assistance with low pump flows. Blood went through pulmonary circulation with CPAD whereas VA ECMO bypassed pulmonary circulation and diminished univentricular blood flow (0.8 L/min). This in silico study demonstrated that CPAD preserved heart/lung function whereas VA ECMO had very low univentricular flow, potentially leading to thrombosis or univentricular atrophy.

The adverse events (AEs) associated with AHD implantation and its interaction with the patient circulation system still profoundly impair the short- to mid-term prognosis, patient’s quality of life (QoL) and, in the worst-case scenario, survival rate. As a result, the associated risks significantly limit the use of AHDs to less than 0.5% of the target population. Addressing the AEs is thus the greatest challenge currently faced by device designers.

The mechanical properties of cells are closely related to their physiological functions and states. Analyzing and measuring these properties are beneficial to understanding cell mechanisms. However, most measurement methods only involve the unidirectional analysis of cellular mechanical properties and thus result in the incomplete measurement of these properties. In this study, a microfluidic platform was established, and an innovative microfluidic chip was designed to measure the multiangle cellular mechanical properties by using dielectrophoresis (DEP) force. Three unsymmetrical indium tin oxide (ITO) microelectrodes were designed and combined with the microfluidic chip, which were utilized to generate DEP force and stretch cell from different angles. A series of experiments was performed to measure and analyze the multiangle mechanical properties of red blood cells of mice. This work provided a new tool for the comprehensive and accurate measurement of multiangle cellular mechanical properties. The results may contribute to the exploration of the internal physiological structures of cells and the building of accurate cell models.

The intra-aortic ventricular assist device (IntraVAD) is a miniature intra-aortic axial-flow ventricular assist device (VAD) that works in series with the left ventricle (LV) to assist the compromised heart. Previous in vitro results have shown that the IntraVAD can successfully increase coronary perfusion and offload ventricular volume by operating in reverse-rotation control (RRc) mode. The RRc mode includes forward rotation in systole and reverse rotation (RR) in diastole. It is necessary to derive a new diffuser design that can be used for the bi-directional rotation of the IntraVAD. In this work, a dual-diffuser set (DDS) was proposed to replace the conventional inducer and diffuser upstream and downstream of the pump. The DDS comprised two diffusers, located on both sides of the impeller, omitting the conventional inducer and diffuser. Different configurations of the DDS were designed and manufactured with various combinations of curved and straight blades. All configurations were initially tested in continuous flow, then in a pulsatile mock circulatory loop. A weighted normalized scalar (WNS) was proposed to comprehensively evaluate the hemodynamic effect of the DDS with different configurations. The results show that the maximum of WNS occurred when the upstream diffuser had equal numbers of curved and straight blades and the downstream diffuser had only curved blades. This indicates such a dual-diffuser design for the IntraVAD can give an optimal cardiac assistance potentially improving ventricular contractility, thereby restoring heart function.

Hemolysis is a major concern in blood-circulating devices, which arises due to hydrodynamic loading on red blood cells from ambient flow environment. Hemolysis estimation models have often been used to aid hemocompatibility design. The preponderance of hemolysis models was formulated on the basis of laminar flows. However, flows in blood-circulating devices are rather complex and can be laminar, transitional or turbulent. It is an extrapolation to apply these models to turbulent flows. For the commonly used power-law models, effective stress has often been represented using Reynolds stresses for estimating hemolysis in turbulent flows. This practice tends to overpredict hemolysis. This study focused on the representation of effective stress in power-law models. Through arithmetic manipulations from Navier-Stokes equation, we showed that effective stress can be represented in terms of energy dissipation, which can be readily obtained from CFD simulations. Three cases were tested, including a capillary tube, the FDA benchmark cases of nozzle model and blood pump. The results showed that the representation of effective stress in terms of energy dissipation greatly improved the prediction of hemolysis for a wide range of flow conditions. The improvement increases as Reynolds number increases; the overprediction of hemolysis was reduced by up to two orders of magnitude.

Hemolysis is one of the most challenging issues faced by blood contacting devices. Empirical hemolysis models often relate hemolysis to shear stress and exposure time. These models were generally derived from the experimental results of Couette-type blood shearing devices, with assumption of uniform exposure time and shear stress. This assumption is not strictly valid since neither exposure time nor shear stress is uniform. Hence, this study evaluated the influence of the nonuniform exposure time and rotor eccentricity or run-out on the accuracy of power-law hemolysis models, using both theoretical and CFD analysis. This work first provided a systematic analysis of the flow regime in a typical Couette shearing device, and showed the axial flow component can be regarded as fully developed laminar plane Poiseuille flow. It was found that the influence of nonuniform exposure time is within 4% for several widely used power-law models, which were validated by steady CFD simulations. A theoretical relationship was then built between the rotor run-out and hemolysis. We noticed that the influence of rotor run-out on hemolysis is within 5% for a moderate rotor run-out ratio of 0.2. Next, transient CFD simulations were performed to investigate the influence of rotor run-out on hemolysis with run-out ratios of 0.1 and 0.2. The results showed negligible effects for a moderate run-out ratio of 0.1. However, a run-out ratio of 0.2 led to a significant increase of hemolysis, resulting from back flows induced by the run-out of the rotor. These findings will be of great importance for the improvement of the hemolysis estimation and blood compatibility design.

Right heart failure (RHF) is a serious health issue with increasing incidence and high mortality. Right ventricular assist devices (RVADs) have been used to support the end-stage failing right ventricle (RV). Current RVADs operate in parallel with native RV, which alter blood flow pattern and increase RV afterload, associated with high tension in cardiac muscles and long-term valve complications. We are developing an in-series RVAD for better RV unloading. This article presents a mathematical model to compare the effects of RV unloading and hemodynamic restoration on an overloaded or failing RV. The model was used to simulate both in-series (sRVAD) and in-parallel (pRVAD) (right atrium-pulmonary artery cannulation) support for severe RHF. The results demonstrated that sRVAD more effectively unloads the RV and restores the balance between RV oxygen supply and demand in RHF patients. In comparison to simulated pRVAD and published clinical and in silico studies, the sRVAD was able to provide comparable restoration of key hemodynamic parameters and demonstrated superior afterload and volume reduction. This study concluded that in-series support was able to produce effective afterload reduction and preserve the valve functionality and native blood flow pattern, eliminating complications associated with in-parallel support.

The IntraVAD is a miniature intra-aortic ventricular assist device (VAD) designed to work in series with the compromised left ventricle. A reverse-rotation control (RRc) mode has been developed to increase myocardial perfusion and reduce ventricular volume. The RRc mode includes forward rotation in systole and reverse rotation in diastole, which requires the IntraVAD to periodically reverse its rotational direction in synchrony with the cardiac cycle. This periodic reversal leads to changes in pressure force over the impeller, which makes the entire system less stable. To eliminate the mechanical wear of a contact bearing and provide active control over the axial position of the rotor, a miniature magnetically levitated bearing (i.e., the PM-Coil module) composed of two concentric permanent magnetic (PM) rings and a pair of coils-one on each side-was proposed to provide passive radial and active axial rotor stabilization. In the early design stage, the numerical finite element method (FEM) was used to optimize the geometry of the brushless DC (BLDC) motor and the maglev module, but constructing a new model each time certain design parameters were adjusted required substantial computation time. Because the design criteria for the module had to be modified to account for the magnetic force produced by the motor and for the hemodynamic changes associated with pump operation, a simplified analytic expression was derived for the expected magnetic forces. Suitable bearings could then be designed capable of overcoming these forces without repeating the complicated FEM simulation for the motor. Using this method at the initial design stage can inform the design of the miniature maglev BLDC motor for the proposed pulsatile axial-flow VAD.

The IntraVAD is an intra-aortic left ventricular assist device (LVAD) to be located in the ascending aorta. In order to enhance unloading and promote coronary flow for the left ventricle (LV), an operating mechanism, reverse-rotation control (RRc) mode, has been developed for the IntraVAD and tested in vitro in a mock circulation loop (MCL). The RRc mode consists of forward rotation (FR) and reverse rotation (RR). The synchronization between the IntraVAD and the LV was studied to offload the ventricle more effectively and to improve myocardial perfusion. The percentage time length of the FR period in the cardiac cycle (Tlf) and time offset between the central-lines of the FR period and the LV systole (Toc) are two parameters of the RRc mode that were varied to adjust the synchronization between the IntraVAD and the LV. The ejection fraction (EF), coronary perfusion pressure (CPP), and arterial pulsatility index (API) were measured at different Tlf and Toc values. These hemodynamic results closely correlated to the LV unloading, coronary perfusion, and peripheral arterial pulsatility. The EF, CPP and API were fed into a weighted normalized scalar (WNS) which was implemented to comprehensively evaluate the hemodynamic influence. The WNS result shows that the overall hemodynamic response is more sensitive to the changes in Toc value than Tlf value. The result shows a significant reduction in LV afterload by starting the FR before LV contraction, then switching to RR at the onset of ventricular dilation. The optimal phase shift of -π/5 was found to precede LV contraction, indicating that changes in LV afterload are more sensitive to the phase shift at the start of the ventricular systole than at the end. Thus, a phase advance between intra-aortic pumps and the LV is critical to unload the ventricle and promote myocardial recovery.

Mock heart circulation loops (MHCLs) serve as in-vitro platforms to investigate the physiological interaction between circulatory systems and cardiovascular devices. A mock heart (MH) engineered with silicone walls and helical aramid fibers, to mimic the complex contraction of a natural heart, has been developed to advance the MHCL previously developed in our group. A mock aorta with an anatomical shape enables the evaluation of a cannulation method for ventricular assist devices (VADs) and investigation of the usage of clinical measurement systems like pressure-volume catheters. Ventricle and aorta molds were produced based on MRI data and cast with silicone. Aramid fibers were layered in the silicone ventricle to reproduce ventricle torsion. A rotating hollow shaft was connected to the apex enabling the rotation of the MH and the connection of a VAD. Silicone wall thickness, aramid fiber angle and fiber pitch were varied to generate different MH models. All MH models were placed in a tank filled with variable amounts of water and air simulating the compliance. In this work, physiological ventricular torsion angles (15°-26°) and physiological pressure-volume loops were achieved. This MHCL can serve as a comprehensive testing platform for cardiovascular devices, such as artificial heart valves and cannulation of VADs.

Cardiac recovery has been observed in end-stage heart failure patients with mechanical circulatory support. An intra-aortic ventricular assist device (IntraVAD) is a novel rotary blood pump designed to operate in the ascending aorta behind the aortic valve, working in series with the compromised left ventricle (LV). Such a device requires optimal motion control in order to enhance the myocardial perfusion and thus promote cardiac recovery. Therefore, a reverse-rotating control (RRc) mode has been proposed to increase the mean arterial pressure (MAP) in diastole where the most coronary flow occurs. The RRc mode consists of two motions - forward rotating speed (FS) and reversely rotating speed (RS). The capability of cardiac recovery of three control modes, including `continuous', `on/off ' and `RRc' modes, was evaluated in vitro. Stroke work (SW), ventricular volume, coronary perfusion pressure (CPP), and arterial pulsatility index (API) were used to evaluate LV unloading, myocardial perfusion and arterial pulsatility. The results show that, all three modes increased the LV stroke work (0.98W vs 1.00W vs 1.01W for continuous, on/off and RRc, respectively; baseline 0.9W) and decreased both end-diastolic volume (EDV) and end-systolic volume (ESV). The "RRc" mode improved CPP significantly (78.4 mm Hg compared to 66.4 mmHg and 70.9 mm Hg for continuous and on/off modes; baseline 71 mm Hg). The arterial pulsatility was higher in `RRc' mode (0.84 compared to 0.43 and 0.59; baseline 0.48). In summary, the IntraVAD operating in the RRc mode can successfully unload the LV, enhance the myocardial perfusion, and restore the arterial pulsatility; therefore, it could be a promising therapeutic option to bridge heart failure patients to recovery.

The intra-aortic ventricular assist device (IntraVAD) is a miniature intra-aortic axial-flow ventricular assist device (VAD) that works in series with the left ventricle (LV) to assist the compromised heart. Previous in vitro results have shown that the IntraVAD can successfully increase coronary perfusion and offload ventricular volume by operating in reverse-rotation control (RRc) mode. The RRc mode includes forward rotation in systole and reverse rotation (RR) in diastole. It is necessary to derive a new diffuser design that can be used for the bi-directional rotation of the IntraVAD. In this work, a dual-diffuser set (DDS) was proposed to replace the conventional inducer and diffuser upstream and downstream of the pump. The DDS comprised two diffusers, located on both sides of the impeller, omitting the conventional inducer and diffuser. Different configurations of the DDS were designed and manufactured with various combinations of curved and straight blades. All configurations were initially tested in continuous flow, then in a pulsatile mock circulatory loop. A weighted normalized scalar (WNS) was proposed to comprehensively evaluate the hemodynamic effect of the DDS with different configurations. The results show that the maximum of WNS occurred when the upstream diffuser had equal numbers of curved and straight blades and the downstream diffuser had only curved blades. This indicates such a dual-diffuser design for the IntraVAD can give an optimal cardiac assistance potentially improving ventricular contractility, thereby restoring heart function.

Right heart failure (RHF) is a serious health issue with increasing incidence and high mortality. Right ventricular assist devices (RVADs) have been used to support the end-stage failing right ventricle (RV). Current RVADs operate in parallel with native RV, which alter blood flow pattern and increase RV afterload, associated with high tension in cardiac muscles and long-term valve complications. We are developing an in-series RVAD for better RV unloading. This article presents a mathematical model to compare the effects of RV unloading and hemodynamic restoration on an overloaded or failing RV. The model was used to simulate both in-series (sRVAD) and in-parallel (pRVAD) (right atrium-pulmonary artery cannulation) support for severe RHF. The results demonstrated that sRVAD more effectively unloads the RV and restores the balance between RV oxygen supply and demand in RHF patients. In comparison to simulated pRVAD and published clinical and in silico studies, the sRVAD was able to provide comparable restoration of key hemodynamic parameters and demonstrated superior afterload and volume reduction. This study concluded that in-series support was able to produce effective afterload reduction and preserve the valve functionality and native blood flow pattern, eliminating complications associated with in-parallel support.