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

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

Extra-corporeal membrane oxygenation in aortic surgery and dissection : a systematic review

BACKGROUND Very little is known about the role of extracorporeal membrane oxygenation (ECMO) for the management of patients undergoing major aortic surgery with particular reference to aortic dissection. AIM To review the available literature to determine if there was any evidence. METHODS A systematic literature search through PubMed and EMBASE was undertaken according to specific key words. RESULTS The search resulted in 29 publications relevant to the subject: 1 brief communication, 1 surgical technique report, 1 invited commentary, 1 retrospective case review, 1 observational study, 4 retrospective reviews, 13 case reports and 7 conference abstracts. A total of 194 patients were included in these publications of whom 77 survived. CONCLUSION Although there is no compelling evidence for or against the use of ECMO in major aortic surgery or dissection, it is enough to justify its use in this patient population despite current adverse attitude

How can LVAD support influence ventricular energetics parameters in advanced heart failure patients? A retrospective study

Background and objective: Here we present a retrospective analysis of six heart failure patients previously discussed at a multidisciplinary team meeting. Only three out of six patients underwent LVAD insertion as the most appropriate management option. Methods: We sought to reproduce the baseline conditions of these patients on hospital admission using our cardiovascular software simulator (CARDIOSIM ©). Subsequently, we simulated the effects of LVAD support and drug administration on left and right ventricular energetics parameters. LVAD assistance was delivered by CARDIOSIM ©based on the module reproducing the behaviour of the Berlin Heart INCOR pump. Results: The results of our simulations were in agreement with the multidisciplinary team meeting out- come. The analysis of ventricular energetics parameters based on external work and pressure volume area confirmed LVAD support as a beneficial therapeutic option for the three patients considered eligible for this type of treatment. The effects induced by LVAD support and drugs administration showed specific patterns between the two groups of patients. Conclusion: A quantitative approach with the ability to predict outcome during patient’s assessment may well be an aid and not a substitute for clinical decision-making

Mechano-electric effect and a heart assist device in the synergistic model of cardiac function

The breakdown of cardiac self-organization leads to heart diseases and failure, the number one cause of death worldwide. Within the traditional time-varying elastance model, cardiac self-organization and breakdown cannot be addressed due to its inability to incorporate the dynamics of various feedback mechanisms consistently. To face this challenge, we recently proposed a paradigm shift from the time-varying elastance concept to a synergistic model of cardiac function by integrating mechanical, electric and chemical activity on micro-scale sarcomere and macro-scale heart. In this paper, by using our synergistic model, we investigate the mechano-electric feedback (MEF) which is the effect of mechanical activities on electric activity—one of the important feedback loops in cardiac function. We show that the (dysfunction of) MEF leads to various forms of heart arrhythmias, for instance, causing the electric activity and left-ventricular volume and pressure to oscillate too fast, too slowly, or erratically through periodic doubling bifurcations or ectopic excitations of incommensurable frequencies. This can result in a pathological condition, reminiscent of dilated cardiomyopathy, where a heart cannot contract or relax properly, with an ineffective cardiac pumping and abnormal electric activities. This pathological condition is then shown to be improved by a heart assist device (an axial rotary pump) since the latter tends to increase the stroke volume and aortic pressure while inhibiting the progression (bifurcation) to such a pathological condition. These results highlight a nontrivial effect of a mechanical pump on the electric activity of the heart

IABP versus Impella Support in Cardiogenic Shock: “In Silico” Study

Cardiogenic shock (CS) is part of a clinical syndrome consisting of acute left ventricular failure causing severe hypotension leading to inadequate organ and tissue perfusion. The most commonly used devices to support patients affected by CS are Intra-Aortic Balloon Pump (IABP), Impella 2.5 pump and Extracorporeal Membrane Oxygenation. The aim of this study is the comparison between Impella and IABP using CARDIOSIM© software simulator of the cardiovascular system. The results of the simulations included baseline conditions from a virtual patient in CS followed by IABP assistance in synchronised mode with different driving and vacuum pressures. Subsequently, the same baseline conditions were supported by the Impella 2.5 with different rotational speeds. The percentage variation with respect to baseline conditions was calculated for haemodynamic and energetic variables during IABP and Impella assistance. The Impella pump driven with a rotational speed of 50,000 rpm increased the total flow by 4.36% with a reduction in left ventricular end-diastolic volume (LVEDV) by ≅15% to ≅30%. A reduction in left ventricular end systolic volume (LVESV) by ≅10% to ≅18% (≅12% to ≅33%) was observed with IABP (Impella) assistance. The simulation outcome suggests that assistance with the Impella device leads to higher reduction in LVESV, LVEDV, left ventricular external work and left atrial pressure-volume loop area compared to IABP support

Extensive cardiac infiltrative melanoma

We report an unusual clinical case of a 66-year-old patient with cardiac involvement from a metastatic melanoma, causing the formation of a large right atrial mass with extensive infiltration of the right atrial free wall, the interatrial septum, the coronary sinus, and up to the mitral annulus and posterior wall of the right ventricle, unamendable to complete surgical excision. As secondary cardiac tumors are not part of routine daily clinical practice, we thought that this clinical case would be a good educational opportunity for the practicing clinicians, both specialists and nonspecialists

Delayed repair of aortic dissection in sickle cell anaemia as a combined cardiac and vascular surgical approach

We discuss a patient who presented with a type B aortic dissection with a retrograde progression in the context of sickle cell anaemia. Given the involvement of the superior mesenteric artery and concern for bowel ischaemia, a delayed approach was considered. Subsequently, a frozen elephant trunk was performed in the hybrid theatre with the back-up of the vascular surgeon for mesenteric protection. A technically demanding procedure followed by a prolonged and challenging postoperative course finally led to a successful outcome. We argue that the case presented is an example of how a close cooperation between professionals can offer additional options to treatment based on a mixture of skills and background to achieve the desired outcome

Argatroban anticoagulation for adult extracorporeal membrane oxygenation : a systematic review

Background: Heparin is the widely used anti-coagulation strategy for patients on extracorporeal membrane oxygenation (ECMO). Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin (AT) deficiency preclude the use of heparin requiring utilization of an alternative anticoagulant agent. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban as one of the main agents. We aimed to review the evidence with regard to safety and efficacy of argatroban as a potential definitive alternative to heparin in the adult patient population undergoing ECMO support. Methods: A web-based systematic literature search was performed in Medline (PubMed) and Embase from inception until June 18, 2020. Results: The search identified 13 publications relevant to the target (4 cohort studies and 9 case series). Case reports and case series with less than 3 cases were not included in the qualitative synthesis. The aggregate number of argatroban treated patients on ECMO was n = 307. In the majority of studies argatroban was used as a continuous infusion without loading dose. Starting doses on ECMO varied between 0.05 and 2 μg/kg/min and were titrated to achieve the chosen therapeutic target range. The activated partial thormboplastin time (aPTT) was the anticoagulation parameter used for monitoring purposes in most studies, whereas some utilized the activated clotting time (ACT). Optimal therapeutic targets varied between 43-70 and 60-100 seconds for aPTT and between 150-210 and 180-230 seconds for ACT. Bleeding and thromboembolic complication rates were comparable to patients treated with unfractionated heparin (UFH). Conclusions: Argatroban infusion rates and anticoagulation target ranges showed substantial variations. The rational for divergent dosing and monitoring approaches are discussed in this paper. Argatroban appears to be a potential alternative to UFH in patients requiring ECMO. To definitively establish its safety, efficacy and ideal dosing strategy, larger prospective studies on well-defined patient populations are warranted

Quadricuspid aortic valve : a case report and review of the literature

Quadricuspid aortic valve (QAV) is a rare congenital anomaly that can present as aortic insufficiency later in life. We report a case of aortic regurgitation associated with a QAV, treated by aortic valve replacement. The patient presented with breathlessness, lethargy and peripheral oedema. Echocardiography and cardiac magnetic resonance revealed abnormal aortic valve morphology and coronary angiography was normal. The presence of a quadricuspid aortic valve was confirmed intraoperatively. This was excised and replaced with a bioprosthetic valve and the patient recovered well postoperatively. Importantly, the literature indicates that specific QAV morphology and associated structural abnormalities can lead to complications. Hence, early detection and diagnosis of QAV allows effective treatment. Aortic valve surgery is the definitive treatment strategy in patients with aortic valve regurgitation secondary to QAV. However, the long-term effects and complications of treatment of this condition remains largely unknown