Synergistic Model of Cardiac Function with a Heart Assist Device

The breakdown of cardiac self-organization leads to heart diseases and failure, the number one cause of death worldwide. The left ventricular pressure–volume relation plays a key role in the diagnosis and treatment of heart diseases. Lumped-parameter models combined with pressure–volume loop analysis are very effective in simulating clinical scenarios with a view to treatment optimization and outcome prediction. Unfortunately, often invoked in this analysis is the traditional, time-varying elastance concept, in which the ratio of the ventricular pressure to its volume is prescribed by a periodic function of time, instead of being calculated consistently according to the change in feedback mechanisms (e.g., the lack or breakdown of self-organization) in heart diseases. Therefore, the application of the time-varying elastance for the analysis of left ventricular assist device (LVAD)–heart interactions has been questioned. We propose a paradigm shift from the time-varying elastance concept to a synergistic model of cardiac function by integrating the mechanical, electric, and chemical activity on microscale sarcomere and macroscale heart levels and investigating the effect of an axial rotary pump on a failing heart. We show that our synergistic model works better than the time-varying elastance model in reproducing LVAD–heart interactions with sufficient accuracy to describe the left ventricular pressure–volume relation

Left Ventricular Assist Device Flow Pattern Analysis Using a Novel Model Incorporating Left Ventricular Pulsatility

Our current understanding of flow through the circuit of left ventricular assist device (LVAD), left ventricle and ascending aorta remains incompletely understood. Computational fluid dynamics, which allow for analysis of flow in the cardiovascular system, have been used for this purpose, although current simulation models have failed to fully incorporate the interplay between the pulsatile left ventricle and continuous-flow generated by the LVAD. Flow-through the LVAD is dependent on the interaction between device and patient-specific factors with suboptimal flow patterns evoking increased risk of LVAD-related complications. Computational fluid dynamics can be used to analyze how different pump and patient factors affect flow patterns in the left ventricle and the aorta. Computational fluid dynamics simulations were carried out on a patient with a HeartMate II. Simulations were also conducted for theoretical scenarios substituting HeartWare HVAD, HeartMate 3 (HM3) in continuous mode and HM3 with Artificial Pulse. An anatomical model of the patient was reconstructed from computed tomography (CT) images, and the LVAD outflow was used as the inflow boundary condition. The LVAD outflow was calculated separately using a lumped-parameter-model of the systemic circulation, which was calibrated to the patient based on the patient-specific ventricular volume change reconstructed from 4 dimensional computed tomography and pulmonary capillary wedge pressure tracings. The LVADs were implemented in the lumped-parameter-model via published pressure head versus flow (H-Q) curves. To quantify the flushing effect, virtual contrast agent was released in the ascending aorta and its flushing over the cycles was quantified. Shear stress acting on the aortic endothelium and shear rate in the bloodstream were also quantified as indicators of normal/abnormal blood flow, especially the latter being a biomarker of platelet activation and hemolysis. LVAD speeds for the HVAD and HM3 were selected to match flow rates for the patient’s HMII (9,000 RPM for HMII, 5,500 RPM for HM3, and 2,200 RPM for HVAD), the cardiac outputs were 5.81 L/min, 5.83 L/min, and 5.92 L/min, respectively. The velocity of blood flow in the outflow cannula was higher in the HVAD than in the two HeartMate pumps with a cycle average (range) of 0.92 m/s (0.78–1.19 m/s), 0.91 m/s (0.86–1.00 m/s), and 1.74 m/s (1.40–2.24 m/s) for HMII, HM3, and HVAD, respectively. Artificial pulse increased the peak flow rate to 9.84 L/min for the HM3 but the overall cardiac output was 5.96 L/min, which was similar to the continuous mode. Artificial pulse markedly decreased blood stagnation in the ascending aorta; after six cardiac cycles, 48% of the blood was flushed out from the ascending aorta under the continuous operation mode while 60% was flushed under artificial pulse. Shear stress and shear rate in the aortic arch were higher with the HVAD compared to the HMII and HM3, respectively (shear stress: 1.76 vs. 1.33 vs. 1.33 Pa, shear rate: 136 vs. 91.5 vs. 89.4 s–1). Pump-specific factors such as LVAD type and programmed flow algorithms lead to unique flow patterns which influence blood stagnation, shear stress, and platelet activation. The pump-patient interaction can be studied using a novel computational fluid dynamics model to better understand and potentially mitigate the risk of downstream LVAD complications

Development and characterization of the arterial windkessel and its role during left ventricular assist device assistance

Modeling of the cardiovascular system is challenging, but it has the potential to further advance our understanding of normal and pathological conditions. Morphology and function are closely related. The arterial system provides steady blood flow to each organ and damps out wave fluctuations as a consequence of intermittent ventricular ejection. These actions can be approached separately in terms of mathematical relationships between pressure and flow. Lumped parameter models are helpful for the study of the interactions between the heart and the arterial system. The arterial windkessel model still plays a significant role despite its limitations. This review aims to discuss the model and its modifications and derive the fundamental equations by applying electric circuits theory. In addition, its role during left ventricular assist device assistance is explored and discussed in relation to rotary blood pumps

Alternative heart assistance pump

2021 Spring.Includes bibliographical references.On average, the human heart beats around 115,000, and pumps around 2,000 gallons of blood daily. This essential organ may undergo systolic or diastolic dysfunction in which the heart cannot properly contract or relax, respectively. To help hearts pump effectively should these types of failures occur, ventricular assist devices (VAD) are implemented as a temporary or permanent solution. The most common VAD is the left ventricular assist device (LVAD) which supports the left ventricle in pumping the oxygen-rich blood from the heart to the aorta, and ultimately to the rest of the body. Although current VADs are an important treatment for advanced heart failure, generally VADS come with many complications and issues after implantation. These complications include incidents of hemolysis (tearing of the blood cells), thrombosis (clotting of the blood), bleeding (especially in the gastrointestinal tract), and infection at the driveline site. Specifically, the current continuous flow pumps are associated with a much higher incidence of gastrointestinal bleeding, myocardial perfusion, kidney problems, among others, compared with the earlier generation pulsatile pumps. However, the presence of several moving mechanical components made the pulsatile pumps less durable, bulky, and prone to malfunction, ultimately leading to favor toward continuous flow designs. The goal of the present study is to develop a novel heart assist pump, overcoming drawbacks to current commercially available pumps, by improving hemodynamic (blood flow) performance, pulsatility, and eliminating bleeding disorders. Our design will overcome the current pumps which suffer from non-physiological flow, and blood damage. The impact of this work goes beyond heart assist devices and would be applicable to other blood pumps. The fundamental biological and physical principles of designing a blood pump will be reviewed in chapter one. In addition, recent studies on current LVADs and the motivation behind these studies will also be discussed. Then, the idea of using a contractive tubular heart as an alternative pump will be presented in chapter two. To understand the pumping mechanism of the tubular heart, a detailed study on the embryonic heart is presented in this chapter. Subsequently, the effect of flow forces on blood cells will be studied in chapter 3. Moreover, the relation between flow regime and bleeding disorders have been studied in the same chapter. A discussion of our design, including the pump design, testing set up, experimental results will be presented in chapter 4. Finally, the limitations of the present study and future work will be presented in chapter 5

DEVELOPMENT AND IMPLEMENTATION OF NOVEL STRATEGIES TO EXPLOIT 3D ULTRASOUND IMAGING IN CARDIOVASCULAR COMPUTATIONAL BIOMECHANICS

Introduction In the past two decades, major advances have been made in cardiovascular diseases assessment and treatment owing to the advent of sophisticated and more accurate imaging techniques, allowing for better understanding the complexity of 3D anatomical cardiovascular structures1. Volumetric acquisition enables the visualization of cardiac districts from virtually any perspective, better appreciating patient-specific anatomical complexity, as well as an accurate quantitative functional evaluation of chamber volumes and mass avoiding geometric assumptions2. Additionally, this scenario also allowed the evolution from generic to patient-specific 3D cardiac models that, based on in vivo imaging, faithfully represent the anatomy and different cardiac features of a given alive subject, being pivotal either in diagnosis and in planning guidance3. Precise morphological and functional knowledge about either the heart valves\u2019 apparatus and the surrounding structures is crucial when dealing with diagnosis as well as preprocedural planning4. To date, computed tomography (CT) and real-time 3D echocardiography (rt3DE) are typically exploited in this scenario since they allow for encoding comprehensive structural and dynamic information even in the fourth dimension (i.e., time)5,6. However, owing to its cost-effectiveness and very low invasiveness, 3D echocardiography has become the method of choice in most situations for performing the evaluation of cardiac function, developing geometrical models which can provide quantitative anatomical assessment7. Complementing this scenario, computational models have been introduced as numerical engineering tools aiming at adding qualitative and quantitative information on the biomechanical behavior in terms of stress-strain response and other multifactorial parameters8. In particular, over the two last decades, their applications have been ranging from elucidating the heart biomechanics underlying different patho-physiological conditions9 to predicting the effects of either surgical or percutaneous procedures, even comparing several implantation techniques and devices10. At the early stage, most of the studies focused on FE modeling in cardiac environment were based on paradigmatic models11\u201315, being mainly exploited to explore and investigate biomechanical alterations following a specific pathological scenario or again to better understand whether a surgical treatment is better or worse than another one. Differently, nowadays the current generation of computational models heavily exploits the detailed anatomical information yielded by medical imaging to provide patient-specific analyses, paving the way toward the development of virtual surgical-planning tools16\u201319. In this direction, cardiac magnetic resonance (CMR) and CT/micro-CT are the mostly accomplished imaging modality, since they can provide well-defined images thanks to their spatial and temporal resolutions20\u201325. Nonetheless, they cannot be applied routinely in clinical practice, as it can be differently done with rt3DE, progressively became the modality of choice26 since it has no harmful effects on the patient and no radiopaque contrast agent is needed. Despite these advantages, 3D volumetric ultrasound imaging shows intrinsic limitations beyond its limited resolution: i) the deficiency of morphological detail owing to either not so easy achievable detection (e.g., tricuspid valve) or not proper acoustic window, ii) the challenge of tailoring computational models to the patient-specific scenario mimicking the morphology as well as the functionality of the investigated cardiac district (e.g., tethering effect exerted by chordal apparatus in mitral valve insufficiency associated to left ventricular dilation), and iii) the needing to systematically analyse devices performances when dealing with real-life cases where ultrasound imaging is the only performable technique but lacking of standardized acquisition protocol. Main findings In the just described scenario, the main aim of this work was focused on the implementation, development and testing of numerical strategies in order to overcome issues when dealing with 3D ultrasound imaging exploitation towards predictive patient-specific modelling approaches focused on both morphological and biomechanical analyses. Specifically, the first specific objective was the development of a novel approach integrating in vitro imaging and finite element (FE) modeling to evaluate tricuspid valve (TV) biomechanics, facing with the lack of information on anatomical features owing to the clinically evident demanding detection of this anatomical district through in vivo imaging. \u2022 An innovative and semi-automated framework was implemented to generate 3D model of TV, to quantitively describe its 3D morphology and to assess its biomechanical behaviour. At this aim, an image-based in vitro experimental approach was integrated with numerical models based on FE strategy. Experimental measurements directly performed on the benchmark (mock circulation loop) were compared with geometrical features computed on the 3D reconstructed model, pinpointing a global good consistency. Furthermore, obtained realistic reconstructions were used as the input of the FE models, even accounting for proper description of TV leaflets\u2019 anisotropic mechanical response. As done experimentally, simulations reproduced both \u201cincompetent\u201d (FTR) and \u201ccompetent-induced\u201d (PMA), proving the efficiency of such a treatment and suggesting translational potential to the clinic. The second specific aim was the implementation of a computational framework able to reproduce a functionally equivalent model of the mitral valve (MV) sub-valvular apparatus through chordae tendineae topology optimization, aiming at chordae rest length arrangement to be able to include their pre-stress state associated to specific ventricular conformation. \u2022 We sought to establish a framework to build geometrically tractable, functionally equivalent models of the MV chordae tendineae, addressing one of the main topics of the computational scientific literature towards the development of faithful patient-specific models from in vivo imaging. Exploiting the mass spring model (MSM) approach, an iterative tool was proposed aiming to the topology optimization of a paradigmatic chordal apparatus of MVs affected by functional regurgitation, in order to be able to equivalently account for tethering effect exerted by the chordae themselves. The results have shown that the algorithm actually lowered the error between the simulated valve and ground truth data, although the intensity of this improvement is strongly valve-dependent.Finally, the last specific aim was the creation of a numerical strategy able to allow for patient-specific geometrical reconstruction both pre- and post- LVAD implantation, in a specific high-risk clinical scenario being rt3DE the only available imaging technique to be used but without any acquisition protocol. \u2022 We proposed a numerical approach which allowed for a systematic and selective analysis of the mechanism associated to intraventricular thrombus formation and thrombogenic complications in a LVAD-treated dilated left ventricle (LV). Ad-hoc geometry reconstruction workflow was implemented to overcome limitations associated to imaging acquisition in this specific scenario, thus being able to generate computational model of the LV assisted with LVAD. In details, results suggested that blood stasis is influenced either by LVAD flow rate and, to a greater extent, by LV residual contractility, being the positioning of the inflow cannula insertion mandatory to be considered when dealing with LVAD thrombogenic potential assessment

Quasi-static imaged-based immersed boundary-finite element model of human left ventricle in diastole

SUMMARY: Finite stress and strain analyses of the heart provide insight into the biomechanics of myocardial function and dysfunction. Herein, we describe progress toward dynamic patient-specific models of the left ventricle using an immersed boundary (IB) method with a finite element (FE) structural mechanics model. We use a structure-based hyperelastic strain-energy function to describe the passive mechanics of the ventricular myocardium, a realistic anatomical geometry reconstructed from clinical magnetic resonance images of a healthy human heart, and a rule-based fiber architecture. Numerical predictions of this IB/FE model are compared with results obtained by a commercial FE solver. We demonstrate that the IB/FE model yields results that are in good agreement with those of the conventional FE model under diastolic loading conditions, and the predictions of the LV model using either numerical method are shown to be consistent with previous computational and experimental data. These results are among the first to analyze the stress and strain predictions of IB models of ventricular mechanics, and they serve both to verify the IB/FE simulation framework and to validate the IB/FE model. Moreover, this work represents an important step toward using such models for fully dynamic fluid–structure interaction simulations of the heart

Towards patient-specific modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps

Background: Ventricular Assist Devices (VADs) insertion is an established treatment for patients with end-stage heart failure waiting for a heart transplant or in need for long-term circulatory support (destination therapy). Rotary blood pumps (RBP) are the most popular devices in view of their size and performance. Pre-operative planning strategy for the insertion of a left ventricular assist device (LVAD) requires a timely discussion at a Multi-Disciplinary Team Meeting (MDT). Clinical-decision making is based according to the needs of the patient and must be processed without delays. Nevertheless, thrombus formation remains a feared complication which affects outcome. VADs operate in a flow regime which is difficult to simulate: the transitional region at the boundary of laminar and turbulent flow (low Reynolds number). Different methods have been used but the best approach remains debatable. Computational Fluid Dynamics (CFD) is an attractive and invaluable tool for the study of the interactions between VADs and the cardiovascular system. The aim of this thesis is three-fold: a) to investigate the use of pressure-volume analysis in a clinical setting through the review of six heart failure patients previously discussed at a MDT meeting with a view to predict or guide further management; b) to review the theory behind modelling approaches to VADs and their interactions with the cardiovascular system for better understanding of their clinical use. Then, an overview of computational fluid dynamics (CFD) is considered as a prelude to its application to the analysis of VADs performance. Additionally, the development of a simplified model of centrifugal pump will be used in initial simulations as preliminary analysis; c) to examine an example of a proof-of-concept pilot patient-specific model of an axial flow pump (HeartMate II) as pre-operative planning strategy in a patient-specific model with a view to identify potential critical areas that may affect pump function and outcome in a clinical setting. Material and Methods: 3D reconstruction from CT-scan images of patients who underwent the insertion of rotary blood pumps, namely HeartWare HVAD and HeartMate II. Ansys Fluent has been used for CFD analysis based on the fundamental governing equations of motion. Blood has been modelled as incompressible, Newtonian fluid with density = 1060 and viscosity = 0.0035 kg/m-s. The laminar and SST models have been used for comparison purposes. The rotational motion of the impeller has been implemented using the moving reference frame (MRF) approach. The sliding mesh method has also been used to account for unsteady interaction between stationary and moving part. The no-slip condition has been applied to all walls, which were assumed to be rigid. Boundary conditions consisting of velocity inlet and pressure outlet of the pump based on different settings and constant rotational speed for the impeller. Pressure-velocity coupling has been based on the coupled scheme. Spatial discretisation consisted of the “least square cell based” gradient for velocity and “PRESTO” or second order for pressure. Second order upwind has been set for the momentum, turbulent kinetic energy and specific dissipation rate. First order implicit has been set for transient formulation. The pseudo transient algorithm (steady state), the high order relaxation term and the warped-face gradient correction have been used to add an unsteady term to the solution equations with the aim to improve stability and enhance convergence. Specific settings have been considered for comparison purposes. Results: Pressure-volume simulation analysis in six advanced heart failure patients showed that an integrated model of the cardiovascular system based on lumped-parameter representation, modified time-varying elastance and pressure-volume analysis of ventricular function seems a feasible and suitable approach yielding a sufficiently accurate quantitative analysis in real time, therefore applicable within the time-constraints of a clinical setting. Lumped-parameter models consist of simultaneous ordinary differential equations complemented by an algebraic balance equation and are suitable for examination of global distribution of pressure, flow and volume over a range of physiological conditions with inclusion of the interaction between modelled components. Higher level lumped-parameter modelling is needed to address the interaction between the circulation and other systems based on a compromise between complexity and ability to set the required parameters to personalise an integrated lumped-parameter model for a patient-specific approach. CARDIOSIM© fulfils these requirements and does address the systems interaction with its modular approach and assembly of models with varying degree of complexity although 0-D and 1-D coupling may be required for the evaluation of long-term VAD support. The challenge remains the ability to predict outcome over a longer period of time. The preliminary CFD simulations with the HeartWare HVAD centrifugal pump demonstrated that it is possible to obtain an accurate analysis in a timely manner to complement the clinical review process. The simulations with the pilot patient-specific model of the HeartMate II axial flow pump revealed that a complex 3D reconstruction is feasible in a timely manner and can be used to generate sufficiently accurate results to be used in the context of a MDT meeting for the purposes of clinical decision-making. Overall, these three studies demonstrate that the time frame of the simulations was within hours which may fit the time constraints of the clinical environment in the context of a MDT meeting. More specifically, it was shown that the laminar model may be used for an initial evaluation of the flow development within the pump. Nonetheless, the k- model offers higher accuracy if the timeline of the clinical setting allows for a longer simulation. Conclusion: This thesis aimed at the understanding of the use of computational modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps. The novelty lays in the use of both pressure-volume simulation analysis and 3D flow dynamics studies in VADs with a view to treatment optimisation and outcome prediction within the time constraints of a clinical setting in the context of a MDT meeting. The clinical significance and the contribution to the field is a more targeted approach for different groups of patients and a more quantitative evaluation in the clinical decision process based on a pro-active co-operation between clinicians and scientists reducing the potential for “guess work”. The results of this thesis are a proof-of-concept as a prelude to a potential future implementation of patient-specific modelling within a clinical setting on a daily basis demonstrating a clear clinical significance and contribution to the field. The proposed approach does not consider modelling and simulation as a substitute for clinical experience but an additional tool to guide therapeutic intervention and complement the clinical decision process in which the clinician remains the ultimate decision-maker. Such an approach may well add a different dimension to the problem of heart failure with potential for high return in terms of patient’s outcome and long-term surveillance. The same principles would be applicable to other cardiovascular problems in line with the current concept of “Team Approach” such as the Heart Team, the Structural Heart Team or the Aortic Team. The present work has taken this concept closer to clinical delivery and has highlighted its potential but further work remains to be done in refining the technique.Background: Ventricular Assist Devices (VADs) insertion is an established treatment for patients with end-stage heart failure waiting for a heart transplant or in need for long-term circulatory support (destination therapy). Rotary blood pumps (RBP) are the most popular devices in view of their size and performance. Pre-operative planning strategy for the insertion of a left ventricular assist device (LVAD) requires a timely discussion at a Multi-Disciplinary Team Meeting (MDT). Clinical-decision making is based according to the needs of the patient and must be processed without delays. Nevertheless, thrombus formation remains a feared complication which affects outcome. VADs operate in a flow regime which is difficult to simulate: the transitional region at the boundary of laminar and turbulent flow (low Reynolds number). Different methods have been used but the best approach remains debatable. Computational Fluid Dynamics (CFD) is an attractive and invaluable tool for the study of the interactions between VADs and the cardiovascular system. The aim of this thesis is three-fold: a) to investigate the use of pressure-volume analysis in a clinical setting through the review of six heart failure patients previously discussed at a MDT meeting with a view to predict or guide further management; b) to review the theory behind modelling approaches to VADs and their interactions with the cardiovascular system for better understanding of their clinical use. Then, an overview of computational fluid dynamics (CFD) is considered as a prelude to its application to the analysis of VADs performance. Additionally, the development of a simplified model of centrifugal pump will be used in initial simulations as preliminary analysis; c) to examine an example of a proof-of-concept pilot patient-specific model of an axial flow pump (HeartMate II) as pre-operative planning strategy in a patient-specific model with a view to identify potential critical areas that may affect pump function and outcome in a clinical setting. Material and Methods: 3D reconstruction from CT-scan images of patients who underwent the insertion of rotary blood pumps, namely HeartWare HVAD and HeartMate II. Ansys Fluent has been used for CFD analysis based on the fundamental governing equations of motion. Blood has been modelled as incompressible, Newtonian fluid with density = 1060 and viscosity = 0.0035 kg/m-s. The laminar and SST models have been used for comparison purposes. The rotational motion of the impeller has been implemented using the moving reference frame (MRF) approach. The sliding mesh method has also been used to account for unsteady interaction between stationary and moving part. The no-slip condition has been applied to all walls, which were assumed to be rigid. Boundary conditions consisting of velocity inlet and pressure outlet of the pump based on different settings and constant rotational speed for the impeller. Pressure-velocity coupling has been based on the coupled scheme. Spatial discretisation consisted of the “least square cell based” gradient for velocity and “PRESTO” or second order for pressure. Second order upwind has been set for the momentum, turbulent kinetic energy and specific dissipation rate. First order implicit has been set for transient formulation. The pseudo transient algorithm (steady state), the high order relaxation term and the warped-face gradient correction have been used to add an unsteady term to the solution equations with the aim to improve stability and enhance convergence. Specific settings have been considered for comparison purposes. Results: Pressure-volume simulation analysis in six advanced heart failure patients showed that an integrated model of the cardiovascular system based on lumped-parameter representation, modified time-varying elastance and pressure-volume analysis of ventricular function seems a feasible and suitable approach yielding a sufficiently accurate quantitative analysis in real time, therefore applicable within the time-constraints of a clinical setting. Lumped-parameter models consist of simultaneous ordinary differential equations complemented by an algebraic balance equation and are suitable for examination of global distribution of pressure, flow and volume over a range of physiological conditions with inclusion of the interaction between modelled components. Higher level lumped-parameter modelling is needed to address the interaction between the circulation and other systems based on a compromise between complexity and ability to set the required parameters to personalise an integrated lumped-parameter model for a patient-specific approach. CARDIOSIM© fulfils these requirements and does address the systems interaction with its modular approach and assembly of models with varying degree of complexity although 0-D and 1-D coupling may be required for the evaluation of long-term VAD support. The challenge remains the ability to predict outcome over a longer period of time. The preliminary CFD simulations with the HeartWare HVAD centrifugal pump demonstrated that it is possible to obtain an accurate analysis in a timely manner to complement the clinical review process. The simulations with the pilot patient-specific model of the HeartMate II axial flow pump revealed that a complex 3D reconstruction is feasible in a timely manner and can be used to generate sufficiently accurate results to be used in the context of a MDT meeting for the purposes of clinical decision-making. Overall, these three studies demonstrate that the time frame of the simulations was within hours which may fit the time constraints of the clinical environment in the context of a MDT meeting. More specifically, it was shown that the laminar model may be used for an initial evaluation of the flow development within the pump. Nonetheless, the k- model offers higher accuracy if the timeline of the clinical setting allows for a longer simulation. Conclusion: This thesis aimed at the understanding of the use of computational modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps. The novelty lays in the use of both pressure-volume simulation analysis and 3D flow dynamics studies in VADs with a view to treatment optimisation and outcome prediction within the time constraints of a clinical setting in the context of a MDT meeting. The clinical significance and the contribution to the field is a more targeted approach for different groups of patients and a more quantitative evaluation in the clinical decision process based on a pro-active co-operation between clinicians and scientists reducing the potential for “guess work”. The results of this thesis are a proof-of-concept as a prelude to a potential future implementation of patient-specific modelling within a clinical setting on a daily basis demonstrating a clear clinical significance and contribution to the field. The proposed approach does not consider modelling and simulation as a substitute for clinical experience but an additional tool to guide therapeutic intervention and complement the clinical decision process in which the clinician remains the ultimate decision-maker. Such an approach may well add a different dimension to the problem of heart failure with potential for high return in terms of patient’s outcome and long-term surveillance. The same principles would be applicable to other cardiovascular problems in line with the current concept of “Team Approach” such as the Heart Team, the Structural Heart Team or the Aortic Team. The present work has taken this concept closer to clinical delivery and has highlighted its potential but further work remains to be done in refining the technique

A novel approach for treating resistant hypertension using a controlled-pump accumulator relief device

Hypertension contributes to cardiovascular morbidity and mortality worldwide. While many hypertensive patients respond to drug therapy, a growing number of these cases are called resistant hypertension (RH), when patients cannot control their blood pressure to goal levels despite the use of multiple antihypertensive medications. While current interventional treatments for RH are based on dealing with the nervous system, there is no existing procedure that considers altering the way in which blood is pumped into the aorta such that to reduce blood pressure. We hypothesize that RH may be controlled by altering the way in which blood is pumped into the aorta. We introduce a novel idea of implementing what we called the accumulator device, which may be classified as a mechanical assist device for the cardiac system. A lumped-parameter model describing the cardiovascular system is presented and validated. The novel idea of accumulator device is also modeled and incorporated with the cardiovascular system model using analogies between the circulatory system, hydraulic systems, and electric circuits. The simulation work of the proposed accumulator device idea reveals promising preliminary results. It shows an ability to significantly decrease the systolic pressure by regulating the way in which blood is pumped into the aorta during the cardiac cycle, without reducing the cardiac output. It is our hope that this novel approach provides a transformational alternative to existing methods for treating RH, becomes a successful treatment option in the future, and improves life for millions of RH patients.Includes bibliographical reference

Experimental study of the mechanics of the intra-aortic balloon

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis deals with the mechanics of the Intra-Aortic Balloon Pump (IABP), the most widely used temporary cardiac assist device, whose beneficial action is based on the principle of counterpulsation. The investigation is carried out in vitro in increasingly more realistic setups, including a mock circulatory system with physiological distribution of peripheral resistance and compliance in which IABP counterpulsation was simulated. Pressure and flow measurements show the effect of variables such as intra-luminal pressure, angle and aortic compliance on balloon hemodynamics. These data are complemented by results on the duration of balloon inflation and deflation obtained by means of high-speed camera visualisation. Furthermore, wave intensity analysis is carried out and it is identified as a possible alternative method for the assessment of IABP performance. This work includes two prototypes of intra-aortic balloons of novel shape with the balloon chamber tapering both from and toward the balloon tip. In clinical terms, with reference to the semi-recumbent position in which patients assisted with the IABP are nursed in the intensive care unit, the results presented in this thesis indicate that operating the balloon at an angle compromises the benefit of counterpulsation when assessed in vitro